Pub Date : 2025-02-15DOI: 10.1186/s12943-025-02226-9
Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M. Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K. Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor–positive, HER2–negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers. Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, pleural effusions, ascites, and bone. InferCNV distinguished tumor cells, and functional analysis utilized the Molecular Signatures Database. LP tumors displayed enhanced Myc, EMT, TNF-α, and inflammatory pathways compared to those EP tumors. Samples from BL and LP responders showed increased tumor-infiltrating CD8+ T cells and natural killer (NK) cells compared to EP non-responders. Notably, despite a high frequency of CD8+ T cells in responding tumors, a functional analysis revealed significant upregulation of genes associated with stress and apoptosis in proliferative CD4+ and CD8+ T cells in BL tumors compared to in EP and LP tumors. These genes, including HSP90 and HSPA8, are linked to resistance to PD1/PD-L1 immune checkpoint inhibitors. A ligand-receptor analysis showed enhanced interactions associated with inhibitory T-cell proliferation (SPP1-CD44) and suppression of immune activity (MDK-NCL) in LP tumors. Longitudinal biopsies consistently revealed dynamic NK cell expansion and enhanced cytotoxic T cell activity, alongside upregulation of immune activity inhibition, in LP tumors compared to in BL tumors. Notably, the predictive biomarker panel from BL tumor cells was validated in 2 independent cohorts, where it consistently predicted a significant improvement in mPFS duration in signature-high versus -low groups. This study underscores the significance of molecular biomarkers in predicting clinical outcomes to CDK4/6i. Tumor-infiltration CD8+ T and NK cells may also serve as baseline predictors. These insights pave the way for optimizing therapeutic strategies based on microenvironment-specific changes, providing a personalized and effective approach for managing HR+/HER2- mBC and improving patient outcomes.
{"title":"Single-cell RNA sequencing identifies molecular biomarkers predicting late progression to CDK4/6 inhibition in patients with HR+/HER2- metastatic breast cancer","authors":"Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M. Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K. Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi","doi":"10.1186/s12943-025-02226-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02226-9","url":null,"abstract":"Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor–positive, HER2–negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers. Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, pleural effusions, ascites, and bone. InferCNV distinguished tumor cells, and functional analysis utilized the Molecular Signatures Database. LP tumors displayed enhanced Myc, EMT, TNF-α, and inflammatory pathways compared to those EP tumors. Samples from BL and LP responders showed increased tumor-infiltrating CD8+ T cells and natural killer (NK) cells compared to EP non-responders. Notably, despite a high frequency of CD8+ T cells in responding tumors, a functional analysis revealed significant upregulation of genes associated with stress and apoptosis in proliferative CD4+ and CD8+ T cells in BL tumors compared to in EP and LP tumors. These genes, including HSP90 and HSPA8, are linked to resistance to PD1/PD-L1 immune checkpoint inhibitors. A ligand-receptor analysis showed enhanced interactions associated with inhibitory T-cell proliferation (SPP1-CD44) and suppression of immune activity (MDK-NCL) in LP tumors. Longitudinal biopsies consistently revealed dynamic NK cell expansion and enhanced cytotoxic T cell activity, alongside upregulation of immune activity inhibition, in LP tumors compared to in BL tumors. Notably, the predictive biomarker panel from BL tumor cells was validated in 2 independent cohorts, where it consistently predicted a significant improvement in mPFS duration in signature-high versus -low groups. This study underscores the significance of molecular biomarkers in predicting clinical outcomes to CDK4/6i. Tumor-infiltration CD8+ T and NK cells may also serve as baseline predictors. These insights pave the way for optimizing therapeutic strategies based on microenvironment-specific changes, providing a personalized and effective approach for managing HR+/HER2- mBC and improving patient outcomes.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"79 6 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417305","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}
<p><b>Correction: </b><b><i>Mol Cancer </i></b><b>23, 283 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02199-1</b></p><p>Following the publication of the original article [1], the author has requested the publication of an erratum to address the following issues stated below.</p><ul> <li> <p>An article note that says, “Yuanxiang Lao, Yirong Jin, and Songfeng Wu are co-first authors. " should be added to the manuscript.</p> </li> <li> <p>The Supplementary Material 1 should be replaced with the one provided in the Supplementary Informtion in this correction article.</p> </li> <li> <p>The second “Extended data Fig. 3c” should be “Extended data Fig. 3d”, and “Extended Data Fig. 3d” as well as “Extended Data Fig. 3e-f” should be “Extended Data Fig. 3e” and “Extended Data Fig. 3f”, respectively.</p> </li> <li> <p>The figure citation “Extended Data Fig. 5g” should be “Extended Data Fig. 5f”.</p> </li> <li> <p>The figure citation “Extended Data Fig. 8d-e” should be “Extended Data Fig. 8d-g”.</p> </li> </ul><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Lao Y, Jin Y, Wu S, et al. Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma. Mol Cancer. 2024;23:283. https://doi.org/10.1186/s12943-024-02199-1.</p><p>Article CAS 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><span>Author notes</span><ol><li><p>Yuanxiang Lao, Yirong Jin, and Songfeng Wu are co-first authors.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China</p><p>Yuanxiang Lao, Yirong Jin, Ting Fang, Qiang Wang & Beicheng Sun</p></li><li><p>Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Innovative Institute of Tumor Immunity and Medicine (ITIM), Hefei, Anhui, China</p><p>Yuanxiang Lao, Yirong Jin, Ting Fang, Qiang Wang & Beicheng Sun</p></li><li><p>Anhui Provincial Innovation Institute for Pharmaceutical Basic Research, Hefei, Anhui, China</p><p>Yuanxiang Lao, Yirong Jin, Ting Fang, Qiang Wang & Beicheng Sun</p></li><li><p>Beijing Qinglian Biotech Co., Ltd, Beijing, China</p><p>Songfeng Wu & Longqin Sun</p></li></ol><span>Authors</span><ol><li><span>Yuanxiang Lao</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yirong Jin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Songfeng Wu</span>View author publications<p>You can also search for this author in
{"title":"Correction: Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma","authors":"Yuanxiang Lao, Yirong Jin, Songfeng Wu, Ting Fang, Qiang Wang, Longqin Sun, Beicheng Sun","doi":"10.1186/s12943-025-02268-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02268-z","url":null,"abstract":"<p><b>Correction: </b><b><i>Mol Cancer </i></b><b>23, 283 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02199-1</b></p><p>Following the publication of the original article [1], the author has requested the publication of an erratum to address the following issues stated below.</p><ul>\u0000<li>\u0000<p>An article note that says, “Yuanxiang Lao, Yirong Jin, and Songfeng Wu are co-first authors. \" should be added to the manuscript.</p>\u0000</li>\u0000<li>\u0000<p>The Supplementary Material 1 should be replaced with the one provided in the Supplementary Informtion in this correction article.</p>\u0000</li>\u0000<li>\u0000<p>The second “Extended data Fig. 3c” should be “Extended data Fig. 3d”, and “Extended Data Fig. 3d” as well as “Extended Data Fig. 3e-f” should be “Extended Data Fig. 3e” and “Extended Data Fig. 3f”, respectively.</p>\u0000</li>\u0000<li>\u0000<p>The figure citation “Extended Data Fig. 5g” should be “Extended Data Fig. 5f”.</p>\u0000</li>\u0000<li>\u0000<p>The figure citation “Extended Data Fig. 8d-e” should be “Extended Data Fig. 8d-g”.</p>\u0000</li>\u0000</ul><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Lao Y, Jin Y, Wu S, et al. Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma. Mol Cancer. 2024;23:283. https://doi.org/10.1186/s12943-024-02199-1.</p><p>Article CAS 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><span>Author notes</span><ol><li><p>Yuanxiang Lao, Yirong Jin, and Songfeng Wu are co-first authors.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China</p><p>Yuanxiang Lao, Yirong Jin, Ting Fang, Qiang Wang & Beicheng Sun</p></li><li><p>Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Innovative Institute of Tumor Immunity and Medicine (ITIM), Hefei, Anhui, China</p><p>Yuanxiang Lao, Yirong Jin, Ting Fang, Qiang Wang & Beicheng Sun</p></li><li><p>Anhui Provincial Innovation Institute for Pharmaceutical Basic Research, Hefei, Anhui, China</p><p>Yuanxiang Lao, Yirong Jin, Ting Fang, Qiang Wang & Beicheng Sun</p></li><li><p>Beijing Qinglian Biotech Co., Ltd, Beijing, China</p><p>Songfeng Wu & Longqin Sun</p></li></ol><span>Authors</span><ol><li><span>Yuanxiang Lao</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yirong Jin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Songfeng Wu</span>View author publications<p>You can also search for this author in","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"47 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417306","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 : 2025-02-14DOI: 10.1186/s12943-025-02250-9
Sumin Yang, Jieun Seo, Jeonghyeon Choi, Sung-Hyun Kim, Yunmin Kuk, Kyung Chan Park, Mingon Kang, Sangwon Byun, Jae-Yeol Joo
Delving into cancer dormancy has been an inherent task that may drive the lethal recurrence of cancer after primary tumor relief. Cells in quiescence can survive for a short or long term in silence, may undergo genetic or epigenetic changes, and can initiate relapse through certain contextual cues. The state of dormancy can be induced by multiple conditions including cancer drug treatment, in turn, undergoes a life cycle that generally occurs through dissemination, invasion, intravasation, circulation, immune evasion, extravasation, and colonization. Throughout this cascade, a cellular machinery governs the fate of individual cells, largely affected by gene regulation. Despite its significance, a precise view of cancer dormancy is yet hampered. Revolutionizing advanced single cell and long read sequencing through analysis methodologies and artificial intelligence, the most recent stage in the research tool progress, is expected to provide a holistic view of the diverse aspects of cancer dormancy.
{"title":"Towards understanding cancer dormancy over strategic hitching up mechanisms to technologies","authors":"Sumin Yang, Jieun Seo, Jeonghyeon Choi, Sung-Hyun Kim, Yunmin Kuk, Kyung Chan Park, Mingon Kang, Sangwon Byun, Jae-Yeol Joo","doi":"10.1186/s12943-025-02250-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02250-9","url":null,"abstract":"Delving into cancer dormancy has been an inherent task that may drive the lethal recurrence of cancer after primary tumor relief. Cells in quiescence can survive for a short or long term in silence, may undergo genetic or epigenetic changes, and can initiate relapse through certain contextual cues. The state of dormancy can be induced by multiple conditions including cancer drug treatment, in turn, undergoes a life cycle that generally occurs through dissemination, invasion, intravasation, circulation, immune evasion, extravasation, and colonization. Throughout this cascade, a cellular machinery governs the fate of individual cells, largely affected by gene regulation. Despite its significance, a precise view of cancer dormancy is yet hampered. Revolutionizing advanced single cell and long read sequencing through analysis methodologies and artificial intelligence, the most recent stage in the research tool progress, is expected to provide a holistic view of the diverse aspects of cancer dormancy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"10 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418411","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 : 2025-02-14DOI: 10.1186/s12943-025-02257-2
Jie Li, Xinya Gao, Zhanqiang Zhang, Yuanhui Lai, Xunxun Lin, Bo Lin, Maoguang Ma, Xiaoli Liang, Xixi Li, Weiming Lv, Ying Lin, Nu Zhang
<p><b>Correction: Mol Cancer 20, 138 (2021)</b></p><p>https://doi.org/10.1186/s12943-021-01444-1</p><p>Following the publication of the original article [1], the author has requested the publication of an erratum to address the following issues stated below.</p><p> Figure 3 A. Due to the settings of the microscope software, there is a discrepancy between the magnification of the obtained pictures and the actual ones. Therefore, the authors have rearranged the pictures to ensure that all of the images were under the same magnification. Meanwhile, some of the images were wrongly pasted. The corrected figure is shown as below. The authors confirmed that this correction does not affect the conclusion</p><p> Original Fig. 3A:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig1_HTML.png?as=webp" type="image/webp"/><img alt="figure a" aria-describedby="Figa" height="177" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig1_HTML.png" width="685"/></picture></figure><p><b>Corrected Fig. 3A</b>:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig2_HTML.png?as=webp" type="image/webp"/><img alt="figure b" aria-describedby="Figb" height="171" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig2_HTML.png" width="685"/></picture></figure><p> Figure 8 B. IHC (C-myc) from different tumors samples were saved in the same folder. During Figure assembly, the representative image of BT-549 was wrongly pasted. The corrected figure is shown as below. The authors confirmed that this correction does not affect the conclusion</p><p> Original Fig. 8B:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig3_HTML.png?as=webp" type="image/webp"/><img alt="figure c" aria-describedby="Figc" height="200" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig3_HTML.png" width="685"/></picture></figure><p> Corrected Fig. 8B:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig4_HTML.png?as=webp" type="image/webp"/><img alt="figure d" aria-describedby="Figd" height="195" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig4_HTML.png" width="685"/></picture></figure><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Li J, Gao X, Zhang Z, et al. CircCD44 p
{"title":"Correction: CircCD44 plays oncogenic roles in triple-negative breast cancer by modulating the miR-502–5p/KRAS and IGF2BP2/Myc axes","authors":"Jie Li, Xinya Gao, Zhanqiang Zhang, Yuanhui Lai, Xunxun Lin, Bo Lin, Maoguang Ma, Xiaoli Liang, Xixi Li, Weiming Lv, Ying Lin, Nu Zhang","doi":"10.1186/s12943-025-02257-2","DOIUrl":"https://doi.org/10.1186/s12943-025-02257-2","url":null,"abstract":"<p><b>Correction: Mol Cancer 20, 138 (2021)</b></p><p>https://doi.org/10.1186/s12943-021-01444-1</p><p>Following the publication of the original article [1], the author has requested the publication of an erratum to address the following issues stated below.</p><p> Figure 3 A. Due to the settings of the microscope software, there is a discrepancy between the magnification of the obtained pictures and the actual ones. Therefore, the authors have rearranged the pictures to ensure that all of the images were under the same magnification. Meanwhile, some of the images were wrongly pasted. The corrected figure is shown as below. The authors confirmed that this correction does not affect the conclusion</p><p> Original Fig. 3A:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"177\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig1_HTML.png\" width=\"685\"/></picture></figure><p><b>Corrected Fig. 3A</b>:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig2_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"171\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig2_HTML.png\" width=\"685\"/></picture></figure><p> Figure 8 B. IHC (C-myc) from different tumors samples were saved in the same folder. During Figure assembly, the representative image of BT-549 was wrongly pasted. The corrected figure is shown as below. The authors confirmed that this correction does not affect the conclusion</p><p> Original Fig. 8B:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig3_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure c\" aria-describedby=\"Figc\" height=\"200\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig3_HTML.png\" width=\"685\"/></picture></figure><p> Corrected Fig. 8B:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig4_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure d\" aria-describedby=\"Figd\" height=\"195\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02257-2/MediaObjects/12943_2025_2257_Fig4_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Li J, Gao X, Zhang Z, et al. CircCD44 p","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418412","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 : 2025-02-14DOI: 10.1186/s12943-025-02233-w
Liwen Kuang, Lei Wu, Yongsheng Li
Extracellular vesicles (EVs), nanoscale vesicles secreted by cells, have attracted considerable attention in recent years due to their role in tumor immunomodulation. These vesicles facilitate intercellular communication by transporting proteins, nucleic acids, and other biologically active substances, and they exhibit a dual role in tumor development and immune evasion mechanisms. Specifically, EVs can assist tumor cells in evading immune surveillance and attack by impairing immune cell function or modulating immunosuppressive pathways, thereby promoting tumor progression and metastasis. Conversely, they can also transport and release immunomodulatory factors that stimulate the activation and regulation of the immune system, enhancing the body’s capacity to combat malignant diseases. This dual functionality of EVs presents promising avenues and targets for tumor immunotherapy. By examining the biological characteristics of EVs and their influence on tumor immunity, novel therapeutic strategies can be developed to improve the efficacy and relevance of cancer treatment. This review delineates the complex role of EVs in tumor immunomodulation and explores their potential implications for cancer therapeutic approaches, aiming to establish a theoretical foundation and provide practical insights for the advancement of future EVs-based cancer immunotherapy strategies.
{"title":"Extracellular vesicles in tumor immunity: mechanisms and novel insights","authors":"Liwen Kuang, Lei Wu, Yongsheng Li","doi":"10.1186/s12943-025-02233-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02233-w","url":null,"abstract":"Extracellular vesicles (EVs), nanoscale vesicles secreted by cells, have attracted considerable attention in recent years due to their role in tumor immunomodulation. These vesicles facilitate intercellular communication by transporting proteins, nucleic acids, and other biologically active substances, and they exhibit a dual role in tumor development and immune evasion mechanisms. Specifically, EVs can assist tumor cells in evading immune surveillance and attack by impairing immune cell function or modulating immunosuppressive pathways, thereby promoting tumor progression and metastasis. Conversely, they can also transport and release immunomodulatory factors that stimulate the activation and regulation of the immune system, enhancing the body’s capacity to combat malignant diseases. This dual functionality of EVs presents promising avenues and targets for tumor immunotherapy. By examining the biological characteristics of EVs and their influence on tumor immunity, novel therapeutic strategies can be developed to improve the efficacy and relevance of cancer treatment. This review delineates the complex role of EVs in tumor immunomodulation and explores their potential implications for cancer therapeutic approaches, aiming to establish a theoretical foundation and provide practical insights for the advancement of future EVs-based cancer immunotherapy strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"64 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418413","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}
The activity of neurons in the vicinity of tumors is linked to a spectrum of cellular mechanisms, including the facilitation of tumor cell proliferation, synapse formation, angiogenesis, and macrophage polarization. This review consolidates the current understanding of neuro-oncological regulation, underscoring the nuanced interplay between neurological and oncological processes (termed as Cancer-Neuroscience). First, we elucidated how the nervous system accelerates tumor growth, metastasis, and the tumor microenvironment both directly and indirectly through the action of signaling molecules. Importantly, neural activity is also implicated in modulating the efficacy of therapeutic interventions, including immunotherapy. On the contrary, the nervous system potentially has a suppressive effect on tumorigenesis, further underscoring a dual-edged role of neurons in cancer progression. Consequently, targeting specific signaling molecules within neuro-oncological regulatory pathways could potentially suppress tumor development. Future research is poised to explore the intricate mechanisms governing neuro-tumor interactions more deeply, while concurrently refining treatment strategies for tumors by targeting the crosstalk between cancer and neurons.
{"title":"Hijacking of the nervous system in cancer: mechanism and therapeutic targets","authors":"Yu Zhang, Qili Liao, Xuyang Wen, Jiayan Fan, Tifei Yuan, Xuemei Tong, Renbing Jia, Peiwei Chai, Xianqun Fan","doi":"10.1186/s12943-025-02246-5","DOIUrl":"https://doi.org/10.1186/s12943-025-02246-5","url":null,"abstract":"The activity of neurons in the vicinity of tumors is linked to a spectrum of cellular mechanisms, including the facilitation of tumor cell proliferation, synapse formation, angiogenesis, and macrophage polarization. This review consolidates the current understanding of neuro-oncological regulation, underscoring the nuanced interplay between neurological and oncological processes (termed as Cancer-Neuroscience). First, we elucidated how the nervous system accelerates tumor growth, metastasis, and the tumor microenvironment both directly and indirectly through the action of signaling molecules. Importantly, neural activity is also implicated in modulating the efficacy of therapeutic interventions, including immunotherapy. On the contrary, the nervous system potentially has a suppressive effect on tumorigenesis, further underscoring a dual-edged role of neurons in cancer progression. Consequently, targeting specific signaling molecules within neuro-oncological regulatory pathways could potentially suppress tumor development. Future research is poised to explore the intricate mechanisms governing neuro-tumor interactions more deeply, while concurrently refining treatment strategies for tumors by targeting the crosstalk between cancer and neurons.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"22 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191924","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}
The diagnosis and treatment of non-small cell lung cancer in clinical settings face serious challenges, particularly due to the lack of integration between the two processes, which limit real-time adjustments in treatment plans based on the patient’s condition and drive-up treatment costs. Here, we present a multifunctional pH-sensitive core-shell nanoparticle containing quercetin (QCT), termed AHA@MnP/QCT NPs, designed for the simultaneous diagnosis and treatment of non-small cell lung cancer. Mechanistic studies indicated that QCT and Mn2+ exhibited excellent peroxidase-like (POD-like) activity, catalysing the conversion of endogenous hydrogen peroxide into highly toxic hydroxyl radicals through a Fenton-like reaction, depleting glutathione (GSH), promoting reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum, and inducing ferroptosis. Additionally, Mn2+ could activate the cGAS-STING signalling pathway and promote the maturation of dendritic cells and infiltration of activated T cells, thus inducing tumor immunogenic cell death (ICD). Furthermore, it exhibited effective T2-weighted MRI enhancement for tumor imaging, making them valuable for clinical diagnosis. In vitro and in vivo experiments demonstrated that AHA@MnP/QCT NPs enabled non-invasive imaging and tumor treatment, which presented a one-stone-for-two-birds strategy for combining tumor diagnosis and treatment, with broad potential for clinical application in non-small cell lung cancer therapy.
{"title":"Multimodal lung cancer theranostics via manganese phosphate/quercetin particle","authors":"Chong Qiu, Fei Xia, Qingchao Tu, Huan Tang, Yinan Liu, Hongda Liu, Chen Wang, HaiLu Yao, Linying Zhong, Yuanfeng Fu, Pengbo Guo, Weiqi Chen, Xinyu Zhou, Li Zou, Licheng Gan, Jiawei Yan, Yichong Hou, Junzhe Zhang, Huanhuan Pang, Yuqing Meng, Qiaoli Shi, Guang Han, Xijun Wang, Jigang Wang","doi":"10.1186/s12943-025-02242-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02242-9","url":null,"abstract":"The diagnosis and treatment of non-small cell lung cancer in clinical settings face serious challenges, particularly due to the lack of integration between the two processes, which limit real-time adjustments in treatment plans based on the patient’s condition and drive-up treatment costs. Here, we present a multifunctional pH-sensitive core-shell nanoparticle containing quercetin (QCT), termed AHA@MnP/QCT NPs, designed for the simultaneous diagnosis and treatment of non-small cell lung cancer. Mechanistic studies indicated that QCT and Mn2+ exhibited excellent peroxidase-like (POD-like) activity, catalysing the conversion of endogenous hydrogen peroxide into highly toxic hydroxyl radicals through a Fenton-like reaction, depleting glutathione (GSH), promoting reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum, and inducing ferroptosis. Additionally, Mn2+ could activate the cGAS-STING signalling pathway and promote the maturation of dendritic cells and infiltration of activated T cells, thus inducing tumor immunogenic cell death (ICD). Furthermore, it exhibited effective T2-weighted MRI enhancement for tumor imaging, making them valuable for clinical diagnosis. In vitro and in vivo experiments demonstrated that AHA@MnP/QCT NPs enabled non-invasive imaging and tumor treatment, which presented a one-stone-for-two-birds strategy for combining tumor diagnosis and treatment, with broad potential for clinical application in non-small cell lung cancer therapy. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"22 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083322","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 : 2025-02-03DOI: 10.1186/s12943-024-02198-2
Maria Angelica Freitas-Cortez, Fatemeh Masrorpour, Hong Jiang, Iqbal Mahmud, Yue Lu, Ailing Huang, Lisa K. Duong, Qi Wang, Tiffany A. Voss, Claudia S. Kettlun Leyton, Bo Wei, Wai-Kin Chan, Kevin Lin, Jie Zhang, Efrosini Tsouko, Shonik Ganjoo, Hampartsoum B. Barsoumian, Thomas S. Riad, Yun Hu, Carola Leuschner, Nahum Puebla-Osorio, Jing Wang, Jian Hu, Michael A. Davies, Vinay K. Puduvalli, Cyrielle Billon, Thomas P. Burris, Philip L. Lorenzi, Boyi Gan, James W. Welsh
Cancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 + T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase 3 (Lpcat3), which makes cells more prone to ferroptosis. However, the mechanisms by which cancer cells avoid immunotherapy-mediated ferroptosis are unclear. Our study reveals how cancer cells evade ferroptosis and anti-tumor immunity through the upregulation of fatty acid-binding protein 7 (Fabp7). To explore how cancer cells resist immune cell-mediated ferroptosis, we used a comprehensive range of techniques. We worked with cell lines including PD1-sensitive, PD1-resistant, B16F10, and QPP7 glioblastoma cells, and conducted in vivo studies in syngeneic 129 Sv/Ev, C57BL/6, and conditional knockout mice with Rora deletion specifically in CD8+ T cells, Cd8 cre;Rorafl mice. Methods included mass spectrometry-based lipidomics, targeted lipidomics, Oil Red O staining, Seahorse analysis, quantitative PCR, immunohistochemistry, PPARγ transcription factor assays, ChIP-seq, untargeted lipidomic analysis, ROS assay, ex vivo co-culture of CD8+ T cells with cancer cells, ATAC-seq, RNA-seq, Western blotting, co-immunoprecipitation assay, flow cytometry and Imaging Mass Cytometry. PD1-resistant tumors upregulate Fabp7, driving protective metabolic changes that shield cells from ferroptosis and evade anti-tumor immunity. Fabp7 decreases the transcription of ferroptosis-inducing genes like Lpcat3 and increases the transcription of ferroptosis-protective genes such as Bmal1 through epigenetic reprogramming. Lipidomic profiling revealed that Fabp7 increases triglycerides and monounsaturated fatty acids (MUFAs), which impede lipid peroxidation and ROS generation. Fabp7 also improves mitochondrial function and fatty acid oxidation (FAO), enhancing cancer cell survival. Furthermore, cancer cells increase Fabp7 expression in CD8+ T cells, disrupting circadian clock gene expression and triggering apoptosis through p53 stabilization. Clinical trial data revealed that higher FABP7 expression correlates with poorer overall survival and progression-free survival in patients undergoing immunotherapy. Our study uncovers a novel mechanism by which cancer cells evade immune-mediated ferroptosis through Fabp7 upregulation. This protein reprograms lipid metabolism and disrupts circadian regulation in immune cells, promoting tumor survival and resistance to immunotherapy. Targeting Fabp7 could enhance immunotherapy effectiveness by re-sensitizing resistant tumors to ferroptosis.
{"title":"Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins","authors":"Maria Angelica Freitas-Cortez, Fatemeh Masrorpour, Hong Jiang, Iqbal Mahmud, Yue Lu, Ailing Huang, Lisa K. Duong, Qi Wang, Tiffany A. Voss, Claudia S. Kettlun Leyton, Bo Wei, Wai-Kin Chan, Kevin Lin, Jie Zhang, Efrosini Tsouko, Shonik Ganjoo, Hampartsoum B. Barsoumian, Thomas S. Riad, Yun Hu, Carola Leuschner, Nahum Puebla-Osorio, Jing Wang, Jian Hu, Michael A. Davies, Vinay K. Puduvalli, Cyrielle Billon, Thomas P. Burris, Philip L. Lorenzi, Boyi Gan, James W. Welsh","doi":"10.1186/s12943-024-02198-2","DOIUrl":"https://doi.org/10.1186/s12943-024-02198-2","url":null,"abstract":"Cancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 + T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase 3 (Lpcat3), which makes cells more prone to ferroptosis. However, the mechanisms by which cancer cells avoid immunotherapy-mediated ferroptosis are unclear. Our study reveals how cancer cells evade ferroptosis and anti-tumor immunity through the upregulation of fatty acid-binding protein 7 (Fabp7). To explore how cancer cells resist immune cell-mediated ferroptosis, we used a comprehensive range of techniques. We worked with cell lines including PD1-sensitive, PD1-resistant, B16F10, and QPP7 glioblastoma cells, and conducted in vivo studies in syngeneic 129 Sv/Ev, C57BL/6, and conditional knockout mice with Rora deletion specifically in CD8+ T cells, Cd8 cre;Rorafl mice. Methods included mass spectrometry-based lipidomics, targeted lipidomics, Oil Red O staining, Seahorse analysis, quantitative PCR, immunohistochemistry, PPARγ transcription factor assays, ChIP-seq, untargeted lipidomic analysis, ROS assay, ex vivo co-culture of CD8+ T cells with cancer cells, ATAC-seq, RNA-seq, Western blotting, co-immunoprecipitation assay, flow cytometry and Imaging Mass Cytometry. PD1-resistant tumors upregulate Fabp7, driving protective metabolic changes that shield cells from ferroptosis and evade anti-tumor immunity. Fabp7 decreases the transcription of ferroptosis-inducing genes like Lpcat3 and increases the transcription of ferroptosis-protective genes such as Bmal1 through epigenetic reprogramming. Lipidomic profiling revealed that Fabp7 increases triglycerides and monounsaturated fatty acids (MUFAs), which impede lipid peroxidation and ROS generation. Fabp7 also improves mitochondrial function and fatty acid oxidation (FAO), enhancing cancer cell survival. Furthermore, cancer cells increase Fabp7 expression in CD8+ T cells, disrupting circadian clock gene expression and triggering apoptosis through p53 stabilization. Clinical trial data revealed that higher FABP7 expression correlates with poorer overall survival and progression-free survival in patients undergoing immunotherapy. Our study uncovers a novel mechanism by which cancer cells evade immune-mediated ferroptosis through Fabp7 upregulation. This protein reprograms lipid metabolism and disrupts circadian regulation in immune cells, promoting tumor survival and resistance to immunotherapy. Targeting Fabp7 could enhance immunotherapy effectiveness by re-sensitizing resistant tumors to ferroptosis.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077464","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 : 2025-02-03DOI: 10.1186/s12943-025-02241-w
Andrea Marranci, Zhijie Jiang, Marianna Vitiello, Elena Guzzolino, Laura Comelli, Samanta Sarti, Simone Lubrano, Cinzia Franchin, Ileabett Echevarría-Vargas, Andrea Tuccoli, Alberto Mercatanti, Monica Evangelista, Paolo Sportoletti, Giorgio Cozza, Ettore Luzi, Enrico Capobianco, Jessie Villanueva, Giorgio Arrigoni, Giovanni Signore, Silvia Rocchiccioli, Letizia Pitto, Nicholas Tsinoremas, Laura Poliseno
<p><b>Correction</b><b>: </b><b>Mol Cancer 16, 85 (2017)</b></p><p><b>https://doi.org/10.1186/s12943-017-0645-4</b></p><br/><p>Following the publication of the original article [1], the authors would like to update Figure 8. They noticed that the graph in panel d was erroneously duplicated in panel h during the production process. The incorrect and correct figures are provided below.</p><p>Incorrect Figure 8:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figa_HTML.png?as=webp" type="image/webp"/><img alt="figure a" aria-describedby="Figa" height="942" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figa_HTML.png" width="685"/></picture></figure><p>Correct Figure 8:</p><figure><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figb_HTML.png?as=webp" type="image/webp"/><img alt="figure b" aria-describedby="Figb" height="928" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figb_HTML.png" width="685"/></picture></figure><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Marranci A, Jiang Z, Vitiello M, et al. The landscape of <i>BRAF</i> transcript and protein variants in human cancer. Mol Cancer. 2017;16:85. https://doi.org/10.1186/s12943-017-0645-4.</p><p>Article CAS 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><span>Author notes</span><ol><li><p>Equal contributors</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Oncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy</p><p>Andrea Marranci, Marianna Vitiello, Samanta Sarti, Simone Lubrano, Andrea Tuccoli & Laura Poliseno</p></li><li><p>University of Siena, Siena, Italy</p><p>Andrea Marranci, Samanta Sarti & Simone Lubrano</p></li><li><p>Center for Computational Science, University of Miami, Gables One Tower, Room 600 N, 1320 S. Dixie Highway, Coral Gables, FL, 33146-2926, USA</p><p>Zhijie Jiang, Enrico Capobianco & Nicholas Tsinoremas</p></li><li><p>Scuola Superiore Sant’Anna, Pisa, Italy</p><p>Elena Guzzolino</p></li><li><p>Institute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy</p><p>Marianna Vitiello, Laura Comelli, Alberto Mercatanti, Monica Evangelista, Silvia Rocchiccioli, Letizia Pitto & Laura Poliseno</p></li><li><p>Department of Biomedical Sciences, University of Padova, Padua, Italy</p><p>Cinzia Franchin & Giorgio Arrigoni</p></li
{"title":"Correction: The landscape of BRAF transcript and protein variants in human cancer","authors":"Andrea Marranci, Zhijie Jiang, Marianna Vitiello, Elena Guzzolino, Laura Comelli, Samanta Sarti, Simone Lubrano, Cinzia Franchin, Ileabett Echevarría-Vargas, Andrea Tuccoli, Alberto Mercatanti, Monica Evangelista, Paolo Sportoletti, Giorgio Cozza, Ettore Luzi, Enrico Capobianco, Jessie Villanueva, Giorgio Arrigoni, Giovanni Signore, Silvia Rocchiccioli, Letizia Pitto, Nicholas Tsinoremas, Laura Poliseno","doi":"10.1186/s12943-025-02241-w","DOIUrl":"https://doi.org/10.1186/s12943-025-02241-w","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>Mol Cancer 16, 85 (2017)</b></p><p><b>https://doi.org/10.1186/s12943-017-0645-4</b></p><br/><p>Following the publication of the original article [1], the authors would like to update Figure 8. They noticed that the graph in panel d was erroneously duplicated in panel h during the production process. The incorrect and correct figures are provided below.</p><p>Incorrect Figure 8:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"942\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figa_HTML.png\" width=\"685\"/></picture></figure><p>Correct Figure 8:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"928\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02241-w/MediaObjects/12943_2025_2241_Figb_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Marranci A, Jiang Z, Vitiello M, et al. The landscape of <i>BRAF</i> transcript and protein variants in human cancer. Mol Cancer. 2017;16:85. https://doi.org/10.1186/s12943-017-0645-4.</p><p>Article CAS 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><span>Author notes</span><ol><li><p>Equal contributors</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Oncogenomics Unit, Core Research Laboratory, Istituto Toscano Tumori (ITT), AOUP, CNR-IFC, Via Moruzzi 1, 56124, Pisa, Italy</p><p>Andrea Marranci, Marianna Vitiello, Samanta Sarti, Simone Lubrano, Andrea Tuccoli & Laura Poliseno</p></li><li><p>University of Siena, Siena, Italy</p><p>Andrea Marranci, Samanta Sarti & Simone Lubrano</p></li><li><p>Center for Computational Science, University of Miami, Gables One Tower, Room 600 N, 1320 S. Dixie Highway, Coral Gables, FL, 33146-2926, USA</p><p>Zhijie Jiang, Enrico Capobianco & Nicholas Tsinoremas</p></li><li><p>Scuola Superiore Sant’Anna, Pisa, Italy</p><p>Elena Guzzolino</p></li><li><p>Institute of Clinical Physiology (IFC), CNR, Via Moruzzi 1, 56124, Pisa, Italy</p><p>Marianna Vitiello, Laura Comelli, Alberto Mercatanti, Monica Evangelista, Silvia Rocchiccioli, Letizia Pitto & Laura Poliseno</p></li><li><p>Department of Biomedical Sciences, University of Padova, Padua, Italy</p><p>Cinzia Franchin & Giorgio Arrigoni</p></li","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"8 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077465","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}
P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers. However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially linked to anti-cancer immune response. The precise mechanisms by which SELP influences anti-cancer immunity and its involvement in radiotherapy response in CC, however, remain elusive. To address these gaps, this study analyzed tumor tissue samples from 205 CC patients undergoing radiotherapy, scRNA-seq data from 42,159 cells of eight patients, and bulk RNA-sequencing data from 187 radiotherapy-treated patients. The results revealed that elevated SELP expression in tumor endothelial cells (TECs) was significantly correlated with improved survival outcomes in patients treated with radiotherapy. The SELPhigh group exhibited a prominent enrichment of immune-related pathways, coupled with a diminished enrichment in epithelial cell proliferation and angiogenesis pathways. Notably, this group demonstrated increased infiltration of CD8+ T cells and enhanced expression of chemokine receptors, including ACKR1. Furthermore, our data suggest that SELP+ TECs engage in crosstalk with CD8+ T cells via the ACKR1-CCL5 axis, which is associated with improved radiotherapy efficacy. In conclusion, these findings underscore the pivotal role of SELP+ TEC:CD8+ T cell interactions through the ACKR1-CCL5 pathway in enhancing radiotherapy response in CC. Targeting this crosstalk may offer novel therapeutic strategies to mitigate treatment resistance and improve patient survival.
{"title":"SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer","authors":"Qingyu Huang, Wenhui Yang, Fuhao Wang, Rui Huang, Qian Wang, Xiaohui Li, Tianyu Lei, Shengqin Yue, Wenxue Zou, Qi An, Jinbo Yue, Qinyong Hu, Chao Liu","doi":"10.1186/s12943-025-02244-7","DOIUrl":"https://doi.org/10.1186/s12943-025-02244-7","url":null,"abstract":"P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers. However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially linked to anti-cancer immune response. The precise mechanisms by which SELP influences anti-cancer immunity and its involvement in radiotherapy response in CC, however, remain elusive. To address these gaps, this study analyzed tumor tissue samples from 205 CC patients undergoing radiotherapy, scRNA-seq data from 42,159 cells of eight patients, and bulk RNA-sequencing data from 187 radiotherapy-treated patients. The results revealed that elevated SELP expression in tumor endothelial cells (TECs) was significantly correlated with improved survival outcomes in patients treated with radiotherapy. The SELPhigh group exhibited a prominent enrichment of immune-related pathways, coupled with a diminished enrichment in epithelial cell proliferation and angiogenesis pathways. Notably, this group demonstrated increased infiltration of CD8+ T cells and enhanced expression of chemokine receptors, including ACKR1. Furthermore, our data suggest that SELP+ TECs engage in crosstalk with CD8+ T cells via the ACKR1-CCL5 axis, which is associated with improved radiotherapy efficacy. In conclusion, these findings underscore the pivotal role of SELP+ TEC:CD8+ T cell interactions through the ACKR1-CCL5 pathway in enhancing radiotherapy response in CC. Targeting this crosstalk may offer novel therapeutic strategies to mitigate treatment resistance and improve patient survival.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"28 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077462","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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