Gastrointestinal (GI) cancers represent a significant health burden worldwide. Their incidence continues to increase, and their management remains a clinical challenge. Chimeric antigen receptor (CAR) natural killer (NK) cells have emerged as a promising alternative to CAR-T cells for immunotherapy of GI cancers. Notably, CAR-NK cells offer several advantages, including reduced risk of graft-versus-host disease, lower cytokine release syndrome, and the ability to target cancer cells through both CAR-dependent and natural cytotoxic mechanisms. This review comprehensively discusses the development and applications of CAR-NK cells in the treatment of GI cancers. We explored various sources of NK cells, CAR design strategies, and the current state of CAR-NK cell therapy for GI cancers, highlighting recent preclinical and clinical trials. Additionally, we addressed existing challenges and propose potential strategies to enhance the efficacy and safety of CAR-NK cell therapy. Our findings highlight the potential of CAR-NK cells to revolutionize GI cancer treatment and pave the way for future clinical applications.
胃肠道（GI）癌症是全球范围内的重大健康负担。其发病率持续上升，其治疗仍然是一项临床挑战。嵌合抗原受体（CAR）自然杀伤（NK）细胞已成为CAR-T细胞免疫治疗消化道癌症的理想替代品。值得注意的是，CAR-NK 细胞具有多种优势，包括降低移植物抗宿主疾病的风险、降低细胞因子释放综合征，以及通过 CAR 依赖性和天然细胞毒性机制靶向癌细胞的能力。本综述全面讨论了 CAR-NK 细胞在消化道癌症治疗中的开发和应用。我们探讨了 NK 细胞的各种来源、CAR 设计策略以及 CAR-NK 细胞治疗消化道癌症的现状，重点介绍了最近的临床前和临床试验。此外，我们还探讨了现有的挑战，并提出了提高 CAR-NK 细胞疗法疗效和安全性的潜在策略。我们的研究结果凸显了 CAR-NK 细胞彻底改变消化道癌症治疗的潜力，并为未来的临床应用铺平了道路。
{"title":"CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside","authors":"Xingwang Zhu, Jieyun Xue, Hongzhou Jiang, Dongwei Xue","doi":"10.1186/s12943-024-02151-3","DOIUrl":"https://doi.org/10.1186/s12943-024-02151-3","url":null,"abstract":"Gastrointestinal (GI) cancers represent a significant health burden worldwide. Their incidence continues to increase, and their management remains a clinical challenge. Chimeric antigen receptor (CAR) natural killer (NK) cells have emerged as a promising alternative to CAR-T cells for immunotherapy of GI cancers. Notably, CAR-NK cells offer several advantages, including reduced risk of graft-versus-host disease, lower cytokine release syndrome, and the ability to target cancer cells through both CAR-dependent and natural cytotoxic mechanisms. This review comprehensively discusses the development and applications of CAR-NK cells in the treatment of GI cancers. We explored various sources of NK cells, CAR design strategies, and the current state of CAR-NK cell therapy for GI cancers, highlighting recent preclinical and clinical trials. Additionally, we addressed existing challenges and propose potential strategies to enhance the efficacy and safety of CAR-NK cell therapy. Our findings highlight the potential of CAR-NK cells to revolutionize GI cancer treatment and pave the way for future clinical applications.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1186/s12943-024-02118-4
Akram Ghantous, Semira Gonseth Nusslé, Farah J. Nassar, Natalia Spitz, Alexei Novoloaca, Olga Krali, Eric Nickels, Vincent Cahais, Cyrille Cuenin, Ritu Roy, Shaobo Li, Maxime Caron, Dilys Lam, Peter Daniel Fransquet, John Casement, Gordon Strathdee, Mark S. Pearce, Helen M. Hansen, Hwi-Ho Lee, Yong Sun Lee, Adam J. de Smith, Daniel Sinnett, Siri Eldevik Håberg, Jill A. McKay, Jessica Nordlund, Per Magnus, Terence Dwyer, Richard Saffery, Joseph Leo Wiemels, Monica Cheng Munthe-Kaas, Zdenko Herceg
Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues (n=5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression (n=2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation. This study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy. • Precursors of pediatric acute lymphoblastic leukemia may be of epigenetic origin, detectable since birth and affecting patient prognosis. • These epigenetic precursors can be robust over several years and across several populations, ethnicities and surrogate and target tissues.
癌症是儿童因病死亡的主要原因。白血病是最常见的一种癌症，其病因大多不明。越来越多的证据表明，白血病起源于胎儿时期，当时 DNA 甲基化发生了全球性的重新分布，推动了组织分化。研究人员对小儿前 B 型急性淋巴细胞白血病（pre-B ALL）患者出生、诊断、缓解和复发时的替代组织（血液）和目标组织（骨髓）进行了表观遗传组 DNA 甲基化分析。对从出生到诊断的前瞻性队列和从临床疾病到出生的回顾性研究进行了双盲分析。利用独立的技术和人群进行了验证。在所有受试人群（共 317 例病例和 483 例对照）（包括欧洲和西班牙血统）中，嵌套病例与对照组相比，出生时印迹和免疫调节 VTRNA2-1 甲基化水平过高（FDR<0.05）。VTRNA2-1甲基化在出生后数年的随访中保持稳定，在代用组织、靶组织和其他组织中也保持稳定（n=5,023个组织；30种类型）。在对两个临床队列（共 644 例）的白血病组织进行分析时，诊断时 VTRNA2-1 甲基化水平高于对照组，缓解时恢复到正常水平，复发时又重新升高到对照组水平以上。高甲基化与B ALL前期患者存活率降低和VTRNA2-1表达减少有明显相关性（n=2,294个组织；26种类型），支持VTRNA2-1甲基化的功能和转化作用。这项研究为检测小儿先天性B ALL的出生表观遗传前体提供了概念验证。这些改变可通过不同的技术在三大洲和两个种族中重现，可为早期检测和预后提供生物标志物，并为治疗提供可操作的靶点。- 小儿急性淋巴细胞白血病的前体可能源于表观遗传，从出生时就可检测到，并影响患者的预后。- 这些表观遗传前体可在数年内保持稳定，并跨越多个人群、种族、替代组织和靶组织。
{"title":"Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth","authors":"Akram Ghantous, Semira Gonseth Nusslé, Farah J. Nassar, Natalia Spitz, Alexei Novoloaca, Olga Krali, Eric Nickels, Vincent Cahais, Cyrille Cuenin, Ritu Roy, Shaobo Li, Maxime Caron, Dilys Lam, Peter Daniel Fransquet, John Casement, Gordon Strathdee, Mark S. Pearce, Helen M. Hansen, Hwi-Ho Lee, Yong Sun Lee, Adam J. de Smith, Daniel Sinnett, Siri Eldevik Håberg, Jill A. McKay, Jessica Nordlund, Per Magnus, Terence Dwyer, Richard Saffery, Joseph Leo Wiemels, Monica Cheng Munthe-Kaas, Zdenko Herceg","doi":"10.1186/s12943-024-02118-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02118-4","url":null,"abstract":"Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues (n=5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression (n=2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation. This study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy. • Precursors of pediatric acute lymphoblastic leukemia may be of epigenetic origin, detectable since birth and affecting patient prognosis. • These epigenetic precursors can be robust over several years and across several populations, ethnicities and surrogate and target tissues.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enhancing the efficacy of CD19 CAR-T cell therapy can significantly improve patient outcomes by reducing relapse rates in CD19 + B cell malignancies. Exogenous or transgenic cytokines are often used to boost the expansion and durability of CAR-T cells but pose risks of severe toxicities. A promising approach to address these limitations is to immobilize cytokines on the surface of CAR-T cells using transmembrane (TM) anchor domains. Given IL-7 can enhance T-cell proliferation and antitumor activity, our study developed membrane-bound IL-7 constructs using different TM anchor domains (CD8, CD28 and B7-1). We primarily found that the CD8 TM provided superior anchoring for IL-7 compared to CD28 and B7-1. Moreover, the IL-7 construct with a CD8 TM (IL7/CD8) enhanced naïve T cell proliferation and effector functions, and improved the in vitro and in vivo antitumor activity of CD19 CAR-T cells. Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy.
{"title":"Membrane-bound IL-7 immobilized by the CD8 transmembrane region improves efficacy of CD19 CAR-T cell therapy","authors":"Chaoting Zhang, Ting Liu, Shance Li, Xia Teng, Yuge Zhu, Guanyu Zhang, Huimin Xie, Kang Sun, Jiaxin Tu, Wenjun Yang, Zheming Lu","doi":"10.1186/s12943-024-02154-0","DOIUrl":"https://doi.org/10.1186/s12943-024-02154-0","url":null,"abstract":"Enhancing the efficacy of CD19 CAR-T cell therapy can significantly improve patient outcomes by reducing relapse rates in CD19 + B cell malignancies. Exogenous or transgenic cytokines are often used to boost the expansion and durability of CAR-T cells but pose risks of severe toxicities. A promising approach to address these limitations is to immobilize cytokines on the surface of CAR-T cells using transmembrane (TM) anchor domains. Given IL-7 can enhance T-cell proliferation and antitumor activity, our study developed membrane-bound IL-7 constructs using different TM anchor domains (CD8, CD28 and B7-1). We primarily found that the CD8 TM provided superior anchoring for IL-7 compared to CD28 and B7-1. Moreover, the IL-7 construct with a CD8 TM (IL7/CD8) enhanced naïve T cell proliferation and effector functions, and improved the in vitro and in vivo antitumor activity of CD19 CAR-T cells. Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1186/s12943-024-02094-9
Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A. Calin
Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes. Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR. We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles. MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.
{"title":"MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2","authors":"Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A. Calin","doi":"10.1186/s12943-024-02094-9","DOIUrl":"https://doi.org/10.1186/s12943-024-02094-9","url":null,"abstract":"Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes. Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR. We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles. MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-19DOI: 10.1186/s12943-024-02142-4
Shigao Huang, Min Xu, Xiaojun Deng, Qingyue Da, Miaomiao Li, Hao Huang, Lina Zhao, Linlin Jing, Haibo Wang
Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.
正常组织和免疫器官保护是肿瘤放射治疗过程的关键部分。辐射诱导的免疫器官损伤（RIOD）通过增加氧化应激和炎症反应引起多种副反应，导致肿瘤放射治疗的治愈率不理想。本研究旨在开发一种新型高效的抗辐照纳米粒子，并探索其保护小鼠脾脏组织免受辐射的机制。制备了三苯基膦阳离子 NIT 自由基纳米粒子（NPs-TPP-NIT），并用于保护接受 X 射线照射的小鼠脾脏。研究了脾组织病理学和血液学参数，以评估 NPs-TPP-NIT 对 X 射线辐射的保护作用。蛋白质组学用于鉴定与炎症因子调节相关的差异表达蛋白。此外，还进行了体外和体内实验，以评估 NPs-TPP-NIT 对放射治疗的影响。经 6.0 Gy X 射线照射后，NPs-TPP-NIT 提高了小鼠脾脏中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性，降低了丙二醛水平和活性氧的生成。此外，NPs-TPP-NIT 还能抑制细胞凋亡，阻断半胱氨酸天冬氨酸特异性蛋白酶/蛋白酶的活化，上调 Bcl-2 的表达，下调 Bax 的表达。我们证实，NPs-TPP-NIT 能阻止电离辐射诱导的 IKK/IκB/NF-κB 激活，从而减轻辐射诱导的脾脏炎症损伤。此外，在对小鼠进行肿瘤放疗时，NPs-TPP-NIT 没有表现出明显的毒性，也没有显著的肿瘤保护作用。NPs-TPP-NIT 阻止了 IKK/IκB/NF-κB 信号的活化，减少了促炎因子的分泌，促进了脾脏中抗炎因子的产生，显示了放疗引起的损伤修复能力，而不会降低放疗的治疗效果。这表明，NPs-TPP-NIT 可作为一种潜在的辐射防护药物，保护免疫器官免受辐射损伤。
{"title":"Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation","authors":"Shigao Huang, Min Xu, Xiaojun Deng, Qingyue Da, Miaomiao Li, Hao Huang, Lina Zhao, Linlin Jing, Haibo Wang","doi":"10.1186/s12943-024-02142-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02142-4","url":null,"abstract":"Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R-loops are three-stranded nucleic acid structures composed of an RNA–DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.
R 环是一种三链核酸结构，由一条 RNA-DNA 杂交链和一条移位的 DNA 链组成。它们广泛存在，在调控基因表达、DNA 复制以及 DNA 和组蛋白修饰方面发挥着重要作用。然而，它们的调控机制仍不清楚。随着 R 环检测技术的发展，在癌症模型中观察到了 R 环水平的变化，这种变化往往与转录复制冲突和基因组不稳定性有关。N6-甲基腺苷（m6A）是一种 RNA 表观遗传修饰，通过影响 RNA 定位、剪接、翻译和降解来调控基因表达。通过查阅文献，我们发现带有 m6A 修饰的 R 环与肿瘤的发生和发展有关。本文总结了 R 环和 m6A 修饰在基因调控中的分子机制和检测方法，并回顾了肿瘤学中有关 m6A 修饰 R 环的最新研究。我们的目标是为癌症基因组不稳定性的起源和潜在的靶向治疗策略提供新的见解。
{"title":"R-loops’ m6A modification and its roles in cancers","authors":"Yue Qiu, Changfeng Man, Luyu Zhu, Shiqi Zhang, Xiaoyan Wang, Dandan Gong, Yu Fan","doi":"10.1186/s12943-024-02148-y","DOIUrl":"https://doi.org/10.1186/s12943-024-02148-y","url":null,"abstract":"R-loops are three-stranded nucleic acid structures composed of an RNA–DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1186/s12943-024-02158-w
Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker, Gen Sheng Wu, Wafik S El-Deiry
<p><b>Correction</b><b>: </b><b>Mol Cancer 14, 99 (2015)</b></p><p><b>https://doi.org/10.1186/s12943-015-0346-9</b></p><br/><p>Following publication of the original article [1], the authors reported inadvertent errors in two panels of Figure 3.</p><p>The original Figure 3B shows a duplication of a histological image. The duplicated image has been replaced and the images, as well as their labels, have been accurately arranged in the corrected Figure 3. In addition, the attached corrected Figure 3 revises two time point labels in panel E.</p><p>The following clarification was added to figure legend 3E: “A portion of the control and ONC201/TIC10 results shown for reference were previously published [26].” The corrected and incorrect figures are given below.</p><p>Incorrect Figure 3:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figa_HTML.png?as=webp" type="image/webp"/><img alt="figure a" aria-describedby="Figa" height="743" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figa_HTML.png" width="685"/></picture></figure><p>Correct Figure 3:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figb_HTML.png?as=webp" type="image/webp"/><img alt="figure b" aria-describedby="Figb" height="603" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figb_HTML.png" width="685"/></picture></figure><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Allen JE, Krigsfeld G, Patel L, et al. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer. 2015;14:99. https://doi.org/10.1186/s12943-015-0346-9.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Departments of Medicine, Genetics, and Pharmacology, Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania School of Medicine, Philadelphia, 19104, PA, USA</p><p>Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker & Wafik S El-Deiry</p></li><li><p>Current affiliation: Oncoceutics, Inc., Hummelstown, PA, USA</p><p>Joshua E Allen</p></li><li><p>Department of Medical Oncology and Molecular Therapeutics Program, Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Fox Chase Cancer Center, Philadelphia, 19111, PA, USA</p><p>David T Dicker & Wa
更正：Mol Cancer 14, 99 (2015)https://doi.org/10.1186/s12943-015-0346-9Following，原文章[1]发表后，作者报告了图3两个面板中的无心之失。原图3B显示了一张重复的组织学图像。在更正后的图 3 中，重复的图像已被替换，图像及其标签也已准确排列。此外，附图 3 更正了面板 E 中的两个时间点标签。在图例 3E 中添加了以下说明："对照组和 ONC201/TIC10 的部分结果供参考，这些结果之前已发表[26]"。更正和错误的图如下。错误的图 3：正确的图 3：Allen JE, Krigsfeld G, Patel L, et al. TRAIL 诱导化合物的鉴定突出了小分子 ONC201/TIC10 作为激活 TRAIL 通路的独特抗癌剂的作用。Mol Cancer.2015;14:99. https://doi.org/10.1186/s12943-015-0346-9.Article PubMed PubMed Central Google Scholar Download references作者和所属单位医学、遗传学和药理学系，分子肿瘤学和细胞周期调节实验室，宾夕法尼亚大学医学院，费城，19104，宾夕法尼亚州，美国Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker & Wafik S El-DeiryCurrent affiliation：Oncoceutics, Inc、Hummelstown, PA, USAJoshua E AllenDepartment of Medical Oncology and Molecular Therapeutics Program, Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Fox Chase Cancer Center, Philadelphia, 19111, PA, USDavid T Dicker &；Wafik S El-DeiryDepartment of Pathology, Program in Molecular Biology and Genetics, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201、USAGen Sheng WuAuthorsJoshua E AllenView author publications您也可以在PubMed Google ScholarGabriel KrigsfeldView author publications您也可以在PubMed Google ScholarLuv PatelView author publications您也可以在PubMed Google ScholarLuv PatelView author publications您也可以在PubMed Google ScholarPatrick A Mayes查看作者发表的文章ScholarPatrick A MayesView 作者发表作品您也可以在 PubMed Google ScholarDavid T DickerView 作者发表作品您也可以在 PubMed Google ScholarGen Sheng WuView 作者发表作品您也可以在 PubMed Google ScholarWafik S El-Deiry查看作者发表的文章您也可以在PubMed Google Scholar中搜索该作者通讯作者Wafik S El-Deiry.开放存取 本文采用知识共享署名-非商业性-禁止衍生 4.0 国际许可协议进行许可，该协议允许以任何媒介或格式进行任何非商业性使用、共享、分发和复制，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明您是否修改了许可材料。根据本许可协议，您无权分享源自本文或本文部分内容的改编材料。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的信用栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出了许可使用范围，则您需要直接获得版权所有者的许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsCite this articleAllen, J.E., Krigsfeld, G., Patel, L. et al. Correction：TRAIL诱导化合物的鉴定凸显了小分子 ONC201/TIC10 作为激活 TRAIL 通路的独特抗癌剂的作用。Mol Cancer 23, 233 (2024). https://doi.org/10.1186/s12943-024-02158-wDownload citationPublished: 18 October 2024DOI: https://doi.org/10.1186/s12943-024-02158-wShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"Correction: Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway","authors":"Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker, Gen Sheng Wu, Wafik S El-Deiry","doi":"10.1186/s12943-024-02158-w","DOIUrl":"https://doi.org/10.1186/s12943-024-02158-w","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>Mol Cancer 14, 99 (2015)</b></p><p><b>https://doi.org/10.1186/s12943-015-0346-9</b></p><br/><p>Following publication of the original article [1], the authors reported inadvertent errors in two panels of Figure 3.</p><p>The original Figure 3B shows a duplication of a histological image. The duplicated image has been replaced and the images, as well as their labels, have been accurately arranged in the corrected Figure 3. In addition, the attached corrected Figure 3 revises two time point labels in panel E.</p><p>The following clarification was added to figure legend 3E: “A portion of the control and ONC201/TIC10 results shown for reference were previously published [26].” The corrected and incorrect figures are given below.</p><p>Incorrect Figure 3:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"743\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figa_HTML.png\" width=\"685\"/></picture></figure><p>Correct Figure 3:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"603\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figb_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Allen JE, Krigsfeld G, Patel L, et al. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer. 2015;14:99. https://doi.org/10.1186/s12943-015-0346-9.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Departments of Medicine, Genetics, and Pharmacology, Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania School of Medicine, Philadelphia, 19104, PA, USA</p><p>Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker & Wafik S El-Deiry</p></li><li><p>Current affiliation: Oncoceutics, Inc., Hummelstown, PA, USA</p><p>Joshua E Allen</p></li><li><p>Department of Medical Oncology and Molecular Therapeutics Program, Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Fox Chase Cancer Center, Philadelphia, 19111, PA, USA</p><p>David T Dicker & Wa","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1186/s12943-024-02152-2
Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, Guido Kroemer
<p><b>Correction: Mol Cancer 23 187 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02098-5</b></p><p>Following publication of the original article [1], the authors noticed a minor but significant error in the representation of the author name Tarek Ben Ahmed as “Ben” was captured as given name instead of a family name. Thus, in the online version, the name Tarek Ben Ahmed was mistakenly listed as Ahmed TB instead of Ben Ahmed T. The original article has been corrected.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Montégut L, Liu P, Zhao L. et al. Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance. Mol Cancer. 2024;23:187. https://doi.org/10.1186/s12943-024-02098-5</p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Equipe labellisée par la Ligue Contre le Cancer, Inserm U1138, Paris, France</p><p>Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Hui Pan, Adrien Joseph, Jonathan G. Pol, Isabelle Martins & Guido Kroemer</p></li><li><p>Metabolomics and Cell Biology Platforms, Gustave Roussy Institut, Villejuif, France</p><p>Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Uxía Nogueira-Recalde, Hui Pan, Jonathan G. Pol, Laurence Zitvogel, Isabelle Martins & Guido Kroemer</p></li><li><p>Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, Paris, France</p><p>Léa Montégut, Hui Chen, Lisa Derosa, Julie Le Naour, Hui Pan & Laurence Zitvogel</p></li><li><p>Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China</p><p>Shuai Zhang</p></li><li><p>Equipe Labellisée Par la Ligue Contre le Cancer, Inserm U1015, Gustave Roussy, Villejuif, France</p><p>Lisa Derosa, Marine Fidelle, Laurence Zitvogel & Suzette Delaloge</p></li><li><p>Department of Pharmacological Sciences, University of Piemonte Orientale, Novara, Italia</p><p>Silvia Mingoia</p></li><li><p>Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Profesor Novoa Santos, A Coruña, Spain</p><p>Uxía Nogueira-Recalde</p></li><li><p>Department of Translational Research, Institute Curie Research Center, INSERM U932, PSL Research University, Paris, France</p><p>Rafael Mena-Osuna & Eliane Piaggio</p></li><li><p>Growth Factors, Nutrients and Cancer Group, Molecular Oncology Programme, Centro Nacional de Inv
更正：Mol Cancer 23 187 (2024)https://doi.org/10.1186/s12943-024-02098-5Following 原文[1]发表后，作者注意到在表述作者姓名Tarek Ben Ahmed时出现了一个微小但重要的错误，因为 "Ben "被当作姓氏而不是名字。因此，在网络版中，塔里克-本-艾哈迈德（Tarek Ben Ahmed）被误列为艾哈迈德-塔布（Ahmed TB），而不是本-艾哈迈德-塔布（Ben Ahmed T）。Mol Cancer.2024;23:187. https://doi.org/10.1186/s12943-024-02098-5下载参考文献作者及单位巴黎市立大学索邦大学Cordeliers研究中心，巴黎抗癌联盟Equipe labellisée par la Ligue Contre le Cancer，Inserm U1138，巴黎、FranceLéa Montégut、Peng Liu、Liwei Zhao、María Pérez-Lanzón、Hui Chen、Misha Mao、Shuai Zhang、Julie Le Naour、Flavia Lambertucci、Silvia Mingoia、Uxía Nogueira-Recalde、Hui Pan、Adrien Joseph、Jonathan G．Pol, Isabelle Martins & Guido KroemerMetabolomics and Cell Biology Platforms, Gustave Roussy Institut, Villejuif, FranceLéa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Uxía Nogueira-Recalde, Hui Pan, Jonathan G., J., J., J., J., J., J., J., J.
{"title":"Correction: Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance","authors":"Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, Guido Kroemer","doi":"10.1186/s12943-024-02152-2","DOIUrl":"https://doi.org/10.1186/s12943-024-02152-2","url":null,"abstract":"<p><b>Correction: Mol Cancer 23 187 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02098-5</b></p><p>Following publication of the original article [1], the authors noticed a minor but significant error in the representation of the author name Tarek Ben Ahmed as “Ben” was captured as given name instead of a family name. Thus, in the online version, the name Tarek Ben Ahmed was mistakenly listed as Ahmed TB instead of Ben Ahmed T. The original article has been corrected.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Montégut L, Liu P, Zhao L. et al. Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance. Mol Cancer. 2024;23:187. https://doi.org/10.1186/s12943-024-02098-5</p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Equipe labellisée par la Ligue Contre le Cancer, Inserm U1138, Paris, France</p><p>Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Hui Pan, Adrien Joseph, Jonathan G. Pol, Isabelle Martins & Guido Kroemer</p></li><li><p>Metabolomics and Cell Biology Platforms, Gustave Roussy Institut, Villejuif, France</p><p>Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Uxía Nogueira-Recalde, Hui Pan, Jonathan G. Pol, Laurence Zitvogel, Isabelle Martins & Guido Kroemer</p></li><li><p>Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, Paris, France</p><p>Léa Montégut, Hui Chen, Lisa Derosa, Julie Le Naour, Hui Pan & Laurence Zitvogel</p></li><li><p>Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China</p><p>Shuai Zhang</p></li><li><p>Equipe Labellisée Par la Ligue Contre le Cancer, Inserm U1015, Gustave Roussy, Villejuif, France</p><p>Lisa Derosa, Marine Fidelle, Laurence Zitvogel & Suzette Delaloge</p></li><li><p>Department of Pharmacological Sciences, University of Piemonte Orientale, Novara, Italia</p><p>Silvia Mingoia</p></li><li><p>Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Profesor Novoa Santos, A Coruña, Spain</p><p>Uxía Nogueira-Recalde</p></li><li><p>Department of Translational Research, Institute Curie Research Center, INSERM U932, PSL Research University, Paris, France</p><p>Rafael Mena-Osuna & Eliane Piaggio</p></li><li><p>Growth Factors, Nutrients and Cancer Group, Molecular Oncology Programme, Centro Nacional de Inv","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1186/s12943-024-02150-4
Jae-Hyeok Kang, Nizam Uddin, Seungmo Kim, Yi Zhao, Ki-Chun Yoo, Min-Jung Kim, Sung-Ah Hong, Sangsu Bae, Jeong-Yeon Lee, Incheol Shin, Young Woo Jin, Heather M. O’Hagan, Joo Mi Yi, Su-Jae Lee
Triple-negative breast cancer (TNBC), the most aggressive subtype, presents a critical challenge due to the absence of approved targeted therapies. Hence, there is an urgent need to identify effective therapeutic targets for this condition. While epidermal growth factor receptor (EGFR) is prominently expressed in TNBC and recognized as a therapeutic target, anti-EGFR therapies have yet to gain approval for breast cancer treatment due to their associated side effects and limited efficacy. Here, we discovered that intercellular adhesion molecule-1 (ICAM-1) exhibits elevated expression levels in metastatic breast cancer and serves as a pivotal binding adaptor for EGFR activation, playing a crucial role in malignant progression. The activation of EGFR by tumor-expressed ICAM-1 initiates biased signaling within the JAK1/STAT3 pathway, consequently driving epithelial-to-mesenchymal transition and facilitating heightened metastasis without influencing tumor growth. Remarkably, ICAM-1-neutralizing antibody treatment significantly suppressed cancer metastasis in a breast cancer orthotopic xenograft mouse model. In conclusion, our identification of ICAM-1 as a novel tumor intrinsic regulator of EGFR activation offers valuable insights for the development of TNBC-specific anti-EGFR therapies.
{"title":"Tumor-intrinsic role of ICAM-1 in driving metastatic progression of triple-negative breast cancer through direct interaction with EGFR","authors":"Jae-Hyeok Kang, Nizam Uddin, Seungmo Kim, Yi Zhao, Ki-Chun Yoo, Min-Jung Kim, Sung-Ah Hong, Sangsu Bae, Jeong-Yeon Lee, Incheol Shin, Young Woo Jin, Heather M. O’Hagan, Joo Mi Yi, Su-Jae Lee","doi":"10.1186/s12943-024-02150-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02150-4","url":null,"abstract":"Triple-negative breast cancer (TNBC), the most aggressive subtype, presents a critical challenge due to the absence of approved targeted therapies. Hence, there is an urgent need to identify effective therapeutic targets for this condition. While epidermal growth factor receptor (EGFR) is prominently expressed in TNBC and recognized as a therapeutic target, anti-EGFR therapies have yet to gain approval for breast cancer treatment due to their associated side effects and limited efficacy. Here, we discovered that intercellular adhesion molecule-1 (ICAM-1) exhibits elevated expression levels in metastatic breast cancer and serves as a pivotal binding adaptor for EGFR activation, playing a crucial role in malignant progression. The activation of EGFR by tumor-expressed ICAM-1 initiates biased signaling within the JAK1/STAT3 pathway, consequently driving epithelial-to-mesenchymal transition and facilitating heightened metastasis without influencing tumor growth. Remarkably, ICAM-1-neutralizing antibody treatment significantly suppressed cancer metastasis in a breast cancer orthotopic xenograft mouse model. In conclusion, our identification of ICAM-1 as a novel tumor intrinsic regulator of EGFR activation offers valuable insights for the development of TNBC-specific anti-EGFR therapies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1186/s12943-024-02137-1
Lin Chen, Yu-Xin Xu, Yuan-Shuo Wang, Ying-Ying Ren, Xue-Man Dong, Pu Wu, Tian Xie, Qi Zhang, Jian-Liang Zhou
Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. Keywords such as “prostate cancer”, “tumor microenvironment”, “immune cells”, “vascular system”, “stromal cells”, and “microbiota” were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation.
{"title":"Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota","authors":"Lin Chen, Yu-Xin Xu, Yuan-Shuo Wang, Ying-Ying Ren, Xue-Man Dong, Pu Wu, Tian Xie, Qi Zhang, Jian-Liang Zhou","doi":"10.1186/s12943-024-02137-1","DOIUrl":"https://doi.org/10.1186/s12943-024-02137-1","url":null,"abstract":"Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. Keywords such as “prostate cancer”, “tumor microenvironment”, “immune cells”, “vascular system”, “stromal cells”, and “microbiota” were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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