Pub Date : 2024-11-08DOI: 10.1186/s12885-024-13142-4
Yanxiong Mao, Fei Chen, Zhangqun Ye, Zhouyang Li, Bo Fan, Yimin Zou, Wen Li, Fen Lan
Background: This study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non-small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).
Methods: From January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients' survival status were analyzed.
Results: Squamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).
Conclusion: The study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.
{"title":"Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis.","authors":"Yanxiong Mao, Fei Chen, Zhangqun Ye, Zhouyang Li, Bo Fan, Yimin Zou, Wen Li, Fen Lan","doi":"10.1186/s12885-024-13142-4","DOIUrl":"10.1186/s12885-024-13142-4","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non-small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).</p><p><strong>Methods: </strong>From January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients' survival status were analyzed.</p><p><strong>Results: </strong>Squamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).</p><p><strong>Conclusion: </strong>The study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1366"},"PeriodicalIF":3.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1186/s12885-024-13117-5
Heli Gao, Wuhu Zhang, Zheng Li, Wensheng Liu, Mengqi Liu, Qifeng Zhuo, Yihua Shi, Wenyan Xu, Chenjie Zhou, Yi Qin, Jin Xu, Jie Chen, Xianjun Yu, Xiaowu Xu, Shunrong Ji
Background: Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem).
Method: Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence.
Results: In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001).
Conclusion: Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.
{"title":"Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide.","authors":"Heli Gao, Wuhu Zhang, Zheng Li, Wensheng Liu, Mengqi Liu, Qifeng Zhuo, Yihua Shi, Wenyan Xu, Chenjie Zhou, Yi Qin, Jin Xu, Jie Chen, Xianjun Yu, Xiaowu Xu, Shunrong Ji","doi":"10.1186/s12885-024-13117-5","DOIUrl":"10.1186/s12885-024-13117-5","url":null,"abstract":"<p><strong>Background: </strong>Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem).</p><p><strong>Method: </strong>Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence.</p><p><strong>Results: </strong>In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001).</p><p><strong>Conclusion: </strong>Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1362"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1186/s12885-024-13119-3
Ran Ni, Tianpeng Zhang, Yixuan Mou, Zhiming Hu, Zongting Gu
Purpose: This study aimed to identify the risk factors associated with ampullary duodenal carcinoma (a-DC) and develop a clinical model to dynamically and accurately predict the risk of lymph node metastasis (LNM) in a-DC patients.
Methods: Data from 4077 patients (2004-2020) were extracted from the Surveillance, Epidemiology, and End Results database to form a training cohort, while 173 cases (2010-2020) from Zhejiang Provincial People's Hospital in China were used as an external validation cohort. A reliable LASSO-logistic method was employed to identify independent risk factors for a-DC LNM, and a nomogram was developed based on these factors to assess the risk of a-DC LNM. The nomogram was evaluated using the Akaike information criterion, misclassification error, area under the curve, and likelihood ratio test. Finally, the nomogram's accuracy and generalizability were externally validated..
Results: After screening using LASSO and logistic regression four variables were identified as independent risk factors for a-DC LNM: sex (P < 0.001), tumor size (P < 0.001), grade (P < 0.001), and tumor extension (P < 0.001). The area under the curve of the nomogram was 74.8% in the training group and 88.9% in the external validation group. The calibration curves demonstrated that the LNM predictions made by the nomogram were in satisfactory agreement with the actual observed LNM. Additionally, the decision curve analysis curves indicated effective clinical utility of the nomogram.
Conclusions: A nomogram based on the LASSO-logistic analysis was constructed to predict a-DC LNM, demonstrating good performance and clinical application value.
{"title":"Accurate prediction of the lymph node status in ampullary duodenal carcinoma: potential guidance for clinical management.","authors":"Ran Ni, Tianpeng Zhang, Yixuan Mou, Zhiming Hu, Zongting Gu","doi":"10.1186/s12885-024-13119-3","DOIUrl":"10.1186/s12885-024-13119-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to identify the risk factors associated with ampullary duodenal carcinoma (a-DC) and develop a clinical model to dynamically and accurately predict the risk of lymph node metastasis (LNM) in a-DC patients.</p><p><strong>Methods: </strong>Data from 4077 patients (2004-2020) were extracted from the Surveillance, Epidemiology, and End Results database to form a training cohort, while 173 cases (2010-2020) from Zhejiang Provincial People's Hospital in China were used as an external validation cohort. A reliable LASSO-logistic method was employed to identify independent risk factors for a-DC LNM, and a nomogram was developed based on these factors to assess the risk of a-DC LNM. The nomogram was evaluated using the Akaike information criterion, misclassification error, area under the curve, and likelihood ratio test. Finally, the nomogram's accuracy and generalizability were externally validated..</p><p><strong>Results: </strong>After screening using LASSO and logistic regression four variables were identified as independent risk factors for a-DC LNM: sex (P < 0.001), tumor size (P < 0.001), grade (P < 0.001), and tumor extension (P < 0.001). The area under the curve of the nomogram was 74.8% in the training group and 88.9% in the external validation group. The calibration curves demonstrated that the LNM predictions made by the nomogram were in satisfactory agreement with the actual observed LNM. Additionally, the decision curve analysis curves indicated effective clinical utility of the nomogram.</p><p><strong>Conclusions: </strong>A nomogram based on the LASSO-logistic analysis was constructed to predict a-DC LNM, demonstrating good performance and clinical application value.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1363"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.
Materials and methods: This study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.
Results: Overall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.
Conclusion: RARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.
Trial registration: UMIN-CTR: UMIN000022278, registered on 11th May 2016.
{"title":"Interim analysis of robot-assisted radical hysterectomy in Japan: a multicenter, prospective interventional single-arm clinical trial.","authors":"Hiroe Ito, Yoshihito Yokoyama, Satoru Kyo, Masaki Mandai, Kenzo Kosaka, Hiroaki Kobayashi, Etsuko Miyagi, Mamiko Onuki, Koji Matsumoto, Noriomi Matsumura, Kota Umemura, Hideki Ishikawa, Keiichi Isaka","doi":"10.1186/s12885-024-13090-z","DOIUrl":"10.1186/s12885-024-13090-z","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.</p><p><strong>Materials and methods: </strong>This study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.</p><p><strong>Results: </strong>Overall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.</p><p><strong>Conclusion: </strong>RARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.</p><p><strong>Trial registration: </strong>UMIN-CTR: UMIN000022278, registered on 11th May 2016.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1360"},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1186/s12885-024-13131-7
Shengnan Yang, Junrong Wang, Zhenwu Du, Chunhua Sheng, Qianyu Liu, Xuewei Lao, Donghui Xu, Ying Pan
Objective: The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer.
Methods: The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro.
Results: (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation.
Conclusion: TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.
研究目的本研究的目的是开发一种治疗卵巢癌的新方法,同时研究肿瘤浸润淋巴细胞(TILs)在卵巢癌治疗中的作用。研究的主要目的是建立从卵巢癌组织或腹水中分离肿瘤细胞、淋巴细胞和树突状细胞(DCs)的技术程序。随后,重点是生成树突状细胞-肿瘤浸润淋巴细胞(DC-TILs),这些细胞具有特定的细胞毒性能力,目的是进行靶向治疗干预。通过体外实验研究了 DC-TIL 相互作用对肿瘤细胞的细胞毒性影响。这项研究旨在为未来卵巢癌 TIL 治疗的临床进展提供基础实验见解:实验样本包括来自吉林大学白求恩第三医院妇科的三名患者(年龄在 32 岁至 75 岁之间)的新鲜手术标本和腹水标本。TIL是从实体瘤组织中通过体外分离提取的,而原代肿瘤细胞和DC则是从腹水标本中获得的。从患者肿瘤细胞中提取的肿瘤特异性抗原被用来刺激DCs的成熟。随后,TIL 与抗原刺激的 DC 细胞共同培养。结果:(1)成功地从一名卵巢癌患者的肿瘤组织中扩增获得了 TILs。(2)从卵巢癌患者腹水细胞中成功诱导出 DC。(3) TILs 能显著增强 DC 刺激后肿瘤细胞的细胞毒性:结论:TILs 有能力增强 DC 刺激后针对肿瘤细胞的细胞毒性。
{"title":"An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells.","authors":"Shengnan Yang, Junrong Wang, Zhenwu Du, Chunhua Sheng, Qianyu Liu, Xuewei Lao, Donghui Xu, Ying Pan","doi":"10.1186/s12885-024-13131-7","DOIUrl":"10.1186/s12885-024-13131-7","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer.</p><p><strong>Methods: </strong>The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro.</p><p><strong>Results: </strong>(1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation.</p><p><strong>Conclusion: </strong>TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1364"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: High levels of LLT1 expression have been found in several cancers, where it interacts with CD161 on NK cells to facilitate tumor immune escape. Targeting LLT1 could potentially relieve this inhibitory signal and enhance anti-tumor responses mediated through NK cells. Using the 'The Cancer Genome Atlas' (TCGA) database, we investigated the role of LLT1 in the tumor microenvironment (TME) across various cancers. Identifying such biomarkers could create new therapeutic options for patients in addition to complementing existing immunotherapies.
Methods: LLT1 expression was evaluated in 33 cancers using TCGA transcriptome data. Univariate Cox regression analysis was employed to assess the correlation of LLT1 expression with patient survival. The relationship between LLT1 expression with immune infiltrates, immune gene signatures, and cancer genomic biomarkers (TMB, MSI, and MMR) was also investigated. Immunofluorescence studies were conducted to validate LLT1 expression in tumors. Furthermore, using the CRI iAtlas data, we evaluated LLT1 distribution and its correlation with other immune checkpoint genes in patients non-responsive to existing immune checkpoint therapies across multiple solid cancers.
Results: High expression of LLT1 was observed in 12 cancers, including BRCA, CHOL, ESCA, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, STAD, SARC, and PCPG. In certain cancers like COAD, KICH, and KIRC, high LLT1 expression was associated with poor prognosis. Further analysis revealed that upregulated LLT1 was associated with an abundance of NK and T cell infiltrates in the TME, as well as exhaustive immune biomarkers, and inversely associated with pro-inflammatory and tumor suppressor signatures. High LLT1 expression is also positively correlated with genomic biomarkers in certain cancers. Immunofluorescence studies confirmed moderate to high LLT1 expression in immune-resistant prostate cancer, glioma, ovarian cancer, and immune-sensitive liver cancer cell lines. An independent assessment of clinical cohorts from CRI iAtlas showed a correlation of upregulated LLT1 with multiple immunosuppressive genes in patients non-responsive to current ICIs.
Conclusions: The biomarker analysis revealed a clear association between elevated LLT1 expression and an immunosuppressive TME in patient cohorts from TCGA and clinical databases. Therefore, this study provides a foundation for utilizing LLT1 as a potential target to improve clinical responses in ICI non-responsive patients with upregulated LLT1.
{"title":"Targeting LLT1 as a potential immunotherapy option for cancer patients non-responsive to existing checkpoint therapies in multiple solid tumors.","authors":"Tirtha Mandal, Soorya Gnanasegaran, Golding Rodrigues, Shalini Kashipathi, Anurag Tiwari, Ashvini Kumar Dubey, Sanghamitra Bhattacharjee, Yogendra Manjunath, Subith Krishna, M S Madhusudhan, Maloy Ghosh","doi":"10.1186/s12885-024-13074-z","DOIUrl":"10.1186/s12885-024-13074-z","url":null,"abstract":"<p><strong>Background: </strong>High levels of LLT1 expression have been found in several cancers, where it interacts with CD161 on NK cells to facilitate tumor immune escape. Targeting LLT1 could potentially relieve this inhibitory signal and enhance anti-tumor responses mediated through NK cells. Using the 'The Cancer Genome Atlas' (TCGA) database, we investigated the role of LLT1 in the tumor microenvironment (TME) across various cancers. Identifying such biomarkers could create new therapeutic options for patients in addition to complementing existing immunotherapies.</p><p><strong>Methods: </strong>LLT1 expression was evaluated in 33 cancers using TCGA transcriptome data. Univariate Cox regression analysis was employed to assess the correlation of LLT1 expression with patient survival. The relationship between LLT1 expression with immune infiltrates, immune gene signatures, and cancer genomic biomarkers (TMB, MSI, and MMR) was also investigated. Immunofluorescence studies were conducted to validate LLT1 expression in tumors. Furthermore, using the CRI iAtlas data, we evaluated LLT1 distribution and its correlation with other immune checkpoint genes in patients non-responsive to existing immune checkpoint therapies across multiple solid cancers.</p><p><strong>Results: </strong>High expression of LLT1 was observed in 12 cancers, including BRCA, CHOL, ESCA, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, STAD, SARC, and PCPG. In certain cancers like COAD, KICH, and KIRC, high LLT1 expression was associated with poor prognosis. Further analysis revealed that upregulated LLT1 was associated with an abundance of NK and T cell infiltrates in the TME, as well as exhaustive immune biomarkers, and inversely associated with pro-inflammatory and tumor suppressor signatures. High LLT1 expression is also positively correlated with genomic biomarkers in certain cancers. Immunofluorescence studies confirmed moderate to high LLT1 expression in immune-resistant prostate cancer, glioma, ovarian cancer, and immune-sensitive liver cancer cell lines. An independent assessment of clinical cohorts from CRI iAtlas showed a correlation of upregulated LLT1 with multiple immunosuppressive genes in patients non-responsive to current ICIs.</p><p><strong>Conclusions: </strong>The biomarker analysis revealed a clear association between elevated LLT1 expression and an immunosuppressive TME in patient cohorts from TCGA and clinical databases. Therefore, this study provides a foundation for utilizing LLT1 as a potential target to improve clinical responses in ICI non-responsive patients with upregulated LLT1.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1365"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1186/s12885-024-13129-1
Francisco Cezar Aquino de Moraes, Michele Kreuz, Isabella Christina Amaral de Lara, Artur de Oliveira Macena Lôbo, Rommel Mario Rodríguez Burbano
Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC.
Methods: PubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software.
Results: A total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04-81.49) and 59.58% (95% CI 39.62-76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83-65.45), 46.12% (95% CI 29.44-63.72), and 28.73% (95% CI 16.57-45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85-68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75-75.51) and for TRAEs of grade ≥ 3 was 17.60% (95% CI 12.28 to 24.57).
Conclusions: This systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes.
背景:梅克尔细胞癌(MCC)是一种罕见的侵袭性神经内分泌皮肤癌,其特点是转移率高。新的证据表明,PD-L1/PD1阻断疗法有望成为治疗梅克尔细胞癌的一种选择。然而,人们对这种方法治疗 MCC 的有效性和安全性仍不甚了解。本系统综述和荟萃分析旨在分析PD-1/PD-L1阻断治疗MCC患者的有效性和安全性:方法:检索了PubMed、Cochrane和Embase上对接受PD-1/PD-L1治疗的MCC患者进行评估的研究。估计结果包括总反应率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)和治疗相关不良事件(TRAEs)。我们使用 RStudio v4.4.2 软件进行了荟萃分析:结果:共纳入了 13 项不同研究的 14 篇报告,涉及 615 名患者。中位年龄从 64 岁到 77 岁不等。中位随访时间从 7.9 个月到 59.3 个月不等。24个月和36个月的汇总OS率分别为65.05%(95% CI 44.04-81.49)和59.58%(95% CI 39.62-76.81),6个月、12个月和36个月的汇总PFS率依次为51.78%(95% CI 37.83-65.45)、46.12%(95% CI 29.44-63.72)和28.73%(95% CI 16.57-45.02)。DCR比例为61.65%(95% CI 54.85-68.03),ORR为53.79%(95% CI 47.80-59.68)。任何等级的TRAEs发生率为61.72%(95% CI 45.75-75.51),等级≥3的TRAEs发生率为17.60%(95% CI 12.28-24.57):这项系统综述和荟萃分析显示,接受PD-1/PDL-1治疗的MCC患者表现出持久的应答,并获得持续且有临床意义的生存结果。
{"title":"Efficacy and safety of PD-1/PD-L1 inhibitors in patients with Merkel Cell Carcinoma: a systematic review and Meta-analysis.","authors":"Francisco Cezar Aquino de Moraes, Michele Kreuz, Isabella Christina Amaral de Lara, Artur de Oliveira Macena Lôbo, Rommel Mario Rodríguez Burbano","doi":"10.1186/s12885-024-13129-1","DOIUrl":"10.1186/s12885-024-13129-1","url":null,"abstract":"<p><strong>Background: </strong>Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC.</p><p><strong>Methods: </strong>PubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software.</p><p><strong>Results: </strong>A total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04-81.49) and 59.58% (95% CI 39.62-76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83-65.45), 46.12% (95% CI 29.44-63.72), and 28.73% (95% CI 16.57-45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85-68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75-75.51) and for TRAEs of grade ≥ 3 was 17.60% (95% CI 12.28 to 24.57).</p><p><strong>Conclusions: </strong>This systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1357"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1186/s12885-024-13134-4
Florence Dedey, Josephine Nsaful, Edmund Nartey, Juliana Labi, Nii Armah Adu-Aryee, Christine Kuti, Joe-Nat Clegg-Lamptey
Background: Cervical cancer is one of the commonest female cancers in Ghana. However, it is preventable. Prevention through Human Papilloma Virus immunization and early detection by screening have their foundation in awareness and a good knowledge about the disease. Acquiring the right knowledge about cervical cancer should be earlier rather than later while mindsets are still being formed to translate into the right attitudes and behaviours later in life.
Methodology: An unpaired pre- and post-test quasi experimental study was conducted at two Ghanaian senior high schools. An educational intervention was carried out comprising a drama, PowerPoint lecture, question and answer session and cervical cancer information leaflet distribution. A self-administered questionnaire was given as a pre-test and repeated as a post-test after 3 months. The total score for each domain of knowledge tested was categorized into adequate knowledge (≥ 50%) and inadequate knowledge (< 50%).
Results: The number of participants in the pre- and post-test were 1,107 and 1,276 girls respectively, with average age of 16 years. General knowledge on cervical cancer improved to 94.4% from 73% following the intervention, but only 46.2% said cervical cancer was curable following the education. Knowledge on symptoms improved from 78 to 87.1% and risk factor knowledge improved from 81.8 to 89.3%. After the intervention, 37% from an initial 42% still thought that having sex at a young age (adolescence) was not a risk factor. Screening and prevention knowledge improved from 82.9 to 91% but only 37.2% knew the recommended age to begin screening with pap smears, even after the education. Overall knowledge on cervical cancer after the education significantly improved from 79.1 to 92.3%.
Conclusion: Knowledge of cervical cancer among young girls in two High Schools, improved with the educational intervention. Areas of education to be emphasized are: cervical cancer is curable if diagnosed early, increased risk with early onset of sexual activity, and recommended age to start screening. Educating young girls on cervical cancer increases their awareness and gives them adequate knowledge which should influence their attitudes and behaviour towards cervical cancer in the future. It should be considered for adoption into high school curricula.
{"title":"Assessing the impact of cervical cancer education in two high schools in Ghana.","authors":"Florence Dedey, Josephine Nsaful, Edmund Nartey, Juliana Labi, Nii Armah Adu-Aryee, Christine Kuti, Joe-Nat Clegg-Lamptey","doi":"10.1186/s12885-024-13134-4","DOIUrl":"10.1186/s12885-024-13134-4","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is one of the commonest female cancers in Ghana. However, it is preventable. Prevention through Human Papilloma Virus immunization and early detection by screening have their foundation in awareness and a good knowledge about the disease. Acquiring the right knowledge about cervical cancer should be earlier rather than later while mindsets are still being formed to translate into the right attitudes and behaviours later in life.</p><p><strong>Methodology: </strong>An unpaired pre- and post-test quasi experimental study was conducted at two Ghanaian senior high schools. An educational intervention was carried out comprising a drama, PowerPoint lecture, question and answer session and cervical cancer information leaflet distribution. A self-administered questionnaire was given as a pre-test and repeated as a post-test after 3 months. The total score for each domain of knowledge tested was categorized into adequate knowledge (≥ 50%) and inadequate knowledge (< 50%).</p><p><strong>Results: </strong>The number of participants in the pre- and post-test were 1,107 and 1,276 girls respectively, with average age of 16 years. General knowledge on cervical cancer improved to 94.4% from 73% following the intervention, but only 46.2% said cervical cancer was curable following the education. Knowledge on symptoms improved from 78 to 87.1% and risk factor knowledge improved from 81.8 to 89.3%. After the intervention, 37% from an initial 42% still thought that having sex at a young age (adolescence) was not a risk factor. Screening and prevention knowledge improved from 82.9 to 91% but only 37.2% knew the recommended age to begin screening with pap smears, even after the education. Overall knowledge on cervical cancer after the education significantly improved from 79.1 to 92.3%.</p><p><strong>Conclusion: </strong>Knowledge of cervical cancer among young girls in two High Schools, improved with the educational intervention. Areas of education to be emphasized are: cervical cancer is curable if diagnosed early, increased risk with early onset of sexual activity, and recommended age to start screening. Educating young girls on cervical cancer increases their awareness and gives them adequate knowledge which should influence their attitudes and behaviour towards cervical cancer in the future. It should be considered for adoption into high school curricula.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1359"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1186/s12885-024-13086-9
Facai Cui, Yu Chen, Xiaoyu Wu, Weifeng Zhao
Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.
{"title":"Mesenchymal stem cell-derived exosomes carrying miR-486-5p inhibit glycolysis and cell stemness in colorectal cancer by targeting NEK2.","authors":"Facai Cui, Yu Chen, Xiaoyu Wu, Weifeng Zhao","doi":"10.1186/s12885-024-13086-9","DOIUrl":"10.1186/s12885-024-13086-9","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1356"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}