British Journal of Cancer最新文献_第2页

Clinical significance of circulating macrophage markers across different stages of prostate cancer: highlighting soluble CD163. 循环巨噬细胞标志物在前列腺癌不同分期的临床意义：突出可溶性CD163。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-10-06 DOI: 10.1038/s41416-026-03633-5

Emma B Hansen, Kristian W Antonsen, Mads R Jochumsen, Paul V Salachan, Kirsten Bouchelouche, Torben F Hansen, Palle J S Osther, Ahmed H Zedan, Michael Borre, Holger J Møller, Karina D Sørensen

{"title":"Clinical significance of circulating macrophage markers across different stages of prostate cancer: highlighting soluble CD163.","authors":"Emma B Hansen, Kristian W Antonsen, Mads R Jochumsen, Paul V Salachan, Kirsten Bouchelouche, Torben F Hansen, Palle J S Osther, Ahmed H Zedan, Michael Borre, Holger J Møller, Karina D Sørensen","doi":"10.1038/s41416-026-03633-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03633-5","url":null,"abstract":"Background: The clinical significance of circulating macrophage markers in prostate cancer (PC) is largely unexplored. Here, we hypothesised that serum levels of the macrophage markers CD163 and SIRPα might be associated with disease aggressiveness and hold prognostic potential in PC, where novel prognostic biomarkers are needed.Methods: Soluble CD163 (sCD163) and SIRPα (sSIRPα) were measured in serum by enzyme-linked immunosorbent assays in three PC cohorts representing different disease stages (N = 646 patients in total). Prognostic results in metastatic castration-resistant PC (mCRPC) were validated in an independent cohort (N = 161).Results: Serum levels of sCD163 and sSIRPα were significantly higher in patients with metastatic vs localised PC (p < 0.05). In general, serum sCD163 and sSIRPα levels were not associated with clinical parameters of disease aggressiveness in patients with hormone-sensitive PC (p > 0.05). In mCRPC, high serum sCD163 levels predicted shorter progression-free survival (PFS) on first-line treatment independent of standard clinical parameters in both the training and validation cohort (training: HR: 1.77 (1.12-2.78), p = 0.014; validation: HR: 1.85 (1.15-2.97), p = 0.011).Conclusions: Circulating levels of sCD163 and sSIRPα were increased in patients with metastatic compared to localised PC. Further, higher sCD163 levels predicted worse PFS in mCRPC, suggesting potential as a future minimally-invasive biomarker to aid mCRPC prognostication.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103970","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}

引用次数: 0

Abundant CD8⁺ tumor-infiltrating lymphocytes in glioblastoma harbor distinct exhaustion signatures in potentially reactive subsets. 胶质母细胞瘤中大量的CD8+肿瘤浸润淋巴细胞在潜在的反应亚群中具有明显的衰竭特征。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-10-05 DOI: 10.1038/s41416-026-03619-3

Takanari Okamoto, Ryo Mizuta, Ayako Demachi-Okamura, Daisuke Muraoka, Yasunori Fukushima, Hiromasa Ishihara, Yujia Sun, Yizheng Wang, Reina Nishida, Eiichi Sasaki, Katsuhiro Masago, Kazuhide Onoguchi, Yuki Tanaka, Yoshiko Yamashita, Richard Stratford, Trevor Clancy, Osamu Muto, Chin Leng Tan, Yoshihiro Otani, Yoshinobu Takahashi, Rui Yamaguchi, Edward W Green, Michael Platten, Isao Date, Shota Tanaka, Naoya Hashimoto, Hirokazu Matsushita

{"title":"Abundant CD8+ tumor-infiltrating lymphocytes in glioblastoma harbor distinct exhaustion signatures in potentially reactive subsets.","authors":"Takanari Okamoto, Ryo Mizuta, Ayako Demachi-Okamura, Daisuke Muraoka, Yasunori Fukushima, Hiromasa Ishihara, Yujia Sun, Yizheng Wang, Reina Nishida, Eiichi Sasaki, Katsuhiro Masago, Kazuhide Onoguchi, Yuki Tanaka, Yoshiko Yamashita, Richard Stratford, Trevor Clancy, Osamu Muto, Chin Leng Tan, Yoshihiro Otani, Yoshinobu Takahashi, Rui Yamaguchi, Edward W Green, Michael Platten, Isao Date, Shota Tanaka, Naoya Hashimoto, Hirokazu Matsushita","doi":"10.1038/s41416-026-03619-3","DOIUrl":"https://doi.org/10.1038/s41416-026-03619-3","url":null,"abstract":"Background: The effectiveness of immunotherapy against glioblastoma (GBM) remains limited, suggesting that antigen-specific tumor-infiltrating lymphocytes (TILs) are rare. This study aimed to identify tumor-specific T cells in GBM as the basis for antigen-specific immunotherapy.Methods: Tumor specimens were collected from 56 patients newly diagnosed with IDH-wildtype GBM. In cases showing prominent intratumoral T-cell infiltration, CD3⁺CD8⁺CD4⁻ T cells were sorted for single-cell RNA and T-cell receptor (TCR) sequencing. Integrated analyses were performed using our single-cell dataset from the Aichi Cancer Center (ACC), publicly available GBM TILs datasets (PA), and lung cancer TILs and malignant pleural effusions datasets (LC). Candidate reactive TCRs were identified using an AI-based algorithm.Results: Unsupervised analysis identified a dominant cluster characterized by the strong expression of exhaustion markers, most prominently LAG3, with high TCR clonality. Moreover, LAG3 and CXCL13 expression levels were significantly higher in the ACC TIL-rich subset than the PA dataset. Finally, a prediction algorithm suggested that our TIL-rich subset harbored a markedly higher proportion of potentially reactive T cells than the PA and LC datasets.Conclusions: TILs with marked clonal expansion in certain GBM cases may include potentially reactive T cells with distinct exhaustion features, providing a foundation for the development of antigen-specific and LAG-3-targeted immunotherapies.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104466","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}

引用次数: 0

Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia. 可选剪接异构体的开关影响黑色素瘤、卵巢癌和急性髓性白血病中蛋白质和药物的相互作用。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-10-03 DOI: 10.1038/s41416-026-03638-0

Tülay Karakulak, Holger Moch, Christian von Mering, Abdullah Kahraman

{"title":"Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia.","authors":"Tülay Karakulak, Holger Moch, Christian von Mering, Abdullah Kahraman","doi":"10.1038/s41416-026-03638-0","DOIUrl":"https://doi.org/10.1038/s41416-026-03638-0","url":null,"abstract":"Background: Alternative splicing is a cellular process and a primary source of proteome diversity. Switches in the Most Dominant Transcript (MDT), where the predominantly expressed isoform changes between normal and cancer samples, have been implicated in disrupting protein interaction networks and driving tumour progression. Thus, identifying switching events in MDT isoforms is crucial for discovering diagnostic biomarkers or therapeutic targets.Methods: Here, we present the most comprehensive study on validated MDT-switching events in melanoma, ovarian cancer, and AML.Results: We identified 6114 unique cancer-associated MDTs (cMDTs) across the three cancer types compared to corresponding normal tissue, of which 1707 cMDTs encode transmembrane proteins, and 131 occur at a high frequency (>30%) in at least one cancer cohort. We validated 12.1% of cMDTs using mass spectrometry-based proteomics data, such as the long isoform of ADD3, which we frequently found in ovarian cancer samples. Our analysis revealed that most of these cMDTs lose interactions with protein partners and drug compounds and correlate with switch events in the spliceosome.Conclusion: This study identifies cMDTs that may serve as candidate biomarkers in melanoma, ovarian cancer, and AML, with the potential to improve cancer diagnosis and support clinical decision-making.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104246","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}

引用次数: 0

From initial complete response to recurrence: ENPP1 mutation drives cisplatin resistance through STING/NF-κB/IL-6 axis in hypopharyngeal squamous cell carcinoma. 从最初的完全缓解到复发：ENPP1突变通过STING/NF-κB/IL-6轴驱动下咽鳞状细胞癌的顺铂耐药

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-10-03 DOI: 10.1038/s41416-026-03625-5

Chunyan Hu, Xin Liu, Cuncun Yuan, Lifen Zhang, Ran Yang, Ruoxi Liu, Wanqing Xiang, Run Yang, Qiwen Hu, Min Yu, Jian Chen, Qiang Huang, Duan Ma, Jin Zhang

{"title":"From initial complete response to recurrence: ENPP1 mutation drives cisplatin resistance through STING/NF-κB/IL-6 axis in hypopharyngeal squamous cell carcinoma.","authors":"Chunyan Hu, Xin Liu, Cuncun Yuan, Lifen Zhang, Ran Yang, Ruoxi Liu, Wanqing Xiang, Run Yang, Qiwen Hu, Min Yu, Jian Chen, Qiang Huang, Duan Ma, Jin Zhang","doi":"10.1038/s41416-026-03625-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03625-5","url":null,"abstract":"Background: Induction chemotherapy proves critical in hypopharyngeal squamous cell carcinoma (HPSCC). However, the mechanisms of acquired resistance to induction chemotherapy have not been fully elucidated yet.Methods: Nine patients with HPSCC who showed an initial response to IC followed by progression and had available paired paraffin-embedded tissue samples were retrospectively analysed. Whole exome sequencing and functional validation were performed in both in vivo and in vitro experiments using CRISPR-Cas9-mediated knockout and mutant variant transfection.Results: 66.7% (6/9) of the patients acquired novel mutations during progression. Among the newly emerged variants, alterations in ENPP1, ALK, and ATP10B were notable for potential functional relevance. Specifically, ENPP1 mutations were present in 50% (3/6) of the cases with acquired alterations. Functional assays demonstrated that ENPP1 knockout suppressed malignant phenotypes in vitro, while overexpression of the mutant ENPP1 (c.2596 G > C, p.Glu866Gln) promoted cisplatin resistance, enhanced 2'3'-cGAMP hydrolysis, and increased tumorigenic capacity in xenograft models. Mechanistically, ENPP1 mutation was associated with sustained activation of STING, accompanied by enchanced NF-κB signaling and elevated IL-6 production, ultimately promoting tumor cell survival and cisplatin resistance.Conclusion: Our study identifies ENPP1 mutation as one of the key genetic drivers of recurrence, mediating both chemotherapy resistance and immunomodulation.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103990","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}

引用次数: 0

Retraction Note: miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients 注：miR-29a/b/c通过靶向CDC42对胶质瘤发挥侵袭抑制作用，预测患者预后。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-10-02 DOI: 10.1038/s41416-026-03643-3

Cuijuan Shi, Linlin Ren, Cuiyun Sun, Lin Yu, Xiuwu Bian, Xuexia Zhou, Yanjun Wen, Dan Hua, Shujun Zhao, Wenjun Luo, Run Wang, Chun Rao, Qian Wang, Shizhu Yu

引用次数: 0

CBL in stage II melanoma: considerations of variant interpretation for driver gene designation II期黑色素瘤的CBL：驱动基因指定的变异解释的考虑。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-10-01 DOI: 10.1038/s41416-026-03629-1

Kok-Siong Poon, Evelyn Siew-Chuan Koay

引用次数: 0

Safety and efficacy of ceralasertib, an ATR kinase inhibitor, combined with olaparib: dose escalation in advanced solid tumours and dose expansion in advanced breast cancer. ATR激酶抑制剂ceralasertib联合奥拉帕尼的安全性和有效性：晚期实体瘤剂量递增和晚期乳腺癌剂量扩大

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-09-30 DOI: 10.1038/s41416-026-03601-z

Juanita S Lopez, Seock-Ah Im, Sophie Postel-Vinay, Mario Campone, Anthony B El-Khoueiry, Wassim Abida, Tobias Arkenau, Keun-Wook Lee, Sun Young Rha, Duncan I Jodrell, Rebecca Roylance, Itziar Irurzun-Arana, Gemma N Jones, Natalia Lukashchuk, Christine Stephens, Conor Norris, Arsène-Bienvenu Loembé, Emma Dean, Matthew G Krebs

{"title":"Safety and efficacy of ceralasertib, an ATR kinase inhibitor, combined with olaparib: dose escalation in advanced solid tumours and dose expansion in advanced breast cancer.","authors":"Juanita S Lopez, Seock-Ah Im, Sophie Postel-Vinay, Mario Campone, Anthony B El-Khoueiry, Wassim Abida, Tobias Arkenau, Keun-Wook Lee, Sun Young Rha, Duncan I Jodrell, Rebecca Roylance, Itziar Irurzun-Arana, Gemma N Jones, Natalia Lukashchuk, Christine Stephens, Conor Norris, Arsène-Bienvenu Loembé, Emma Dean, Matthew G Krebs","doi":"10.1038/s41416-026-03601-z","DOIUrl":"https://doi.org/10.1038/s41416-026-03601-z","url":null,"abstract":"Background: Ceralasertib, an ATR inhibitor, is known to exacerbate replication stress induced by the PARP inhibitor (PARPi) olaparib, with the combination having the potential to overcome PARPi resistance in the clinic. This modular Phase 1 study evaluated the combination in advanced solid tumours, including breast cancer.Methods: Dose escalation of ceralasertib alone (Part A1) or with olaparib (Part A2) in patients with all solid tumours was followed by expansion in PARPi-naïve patients with BRCA1/2 m HER2-negative breast cancer (Part B3) or BRCA1/2 wt triple-negative breast cancer (Part B4).Results: Overall, 142 patients were treated. No dose-limiting toxicities occurred in Part A1. Based on haematological safety in Part A2, the combination recommended Phase 2 dose was ceralasertib 160 mg once-daily, days 1-7, plus olaparib 300 mg twice-daily continuously (28-day cycles). In Parts B3 and B4, 36/37 (97.3%) and 24/25 (96.0%) patients had treatment-emergent adverse events (grade ≥3: 16/37 [43.2%], 9/25 [36.0%]; leading to discontinuation: 2/37 [5.4%], 1/25 [4.0%]), and 7 (18.9%) and 3 (12.0%) required ceralasertib dose reductions. Objective response rates were: Part A1, 0%; Part A2, 16.4% (n = 10/61); Part B3, 37.8% (n = 14/37); and Part B4, 0%.Conclusion: In PARPi-naïve patients with BRCA1/2 m HER2-negative breast cancer, ceralasertib-olaparib had generally manageable safety and demonstrated preliminary antitumour activity.Trial registration number: NCT02264678.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104230","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}

引用次数: 0

Neoadjuvant chemotherapy as a bridge to surgery versus direct surgery following SEMS placement in obstructive left-sided colon cancer: a multicenter prospective cohort study. 一项多中心前瞻性队列研究：新辅助化疗作为手术的桥梁，与SEMS放置后的直接手术相比

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-09-29 DOI: 10.1038/s41416-026-03623-7

Yang Shi, Zhi Wei Zhai, Ke Cao, Chun Xiang Ye, Yan Sen Li, Yan Lei Wang, Kai Yan Yang, Zhao Ding, Xu Hua Hu, Yong Dai, Qun Qian, Gui Ying Wang, Zhen Jun Wang, Jia Gang Han

{"title":"Neoadjuvant chemotherapy as a bridge to surgery versus direct surgery following SEMS placement in obstructive left-sided colon cancer: a multicenter prospective cohort study.","authors":"Yang Shi, Zhi Wei Zhai, Ke Cao, Chun Xiang Ye, Yan Sen Li, Yan Lei Wang, Kai Yan Yang, Zhao Ding, Xu Hua Hu, Yong Dai, Qun Qian, Gui Ying Wang, Zhen Jun Wang, Jia Gang Han","doi":"10.1038/s41416-026-03623-7","DOIUrl":"https://doi.org/10.1038/s41416-026-03623-7","url":null,"abstract":"Objective: To investigate the perioperative complications and long-term outcomes of self-expanding metallic stent (SEMS) placement combined with neoadjuvant chemotherapy followed by elective surgery in patients with complete obstructive left-sided colon cancer (COLCC).Methods: A multicenter prospective study enrolled 246 COLCC patients, comparing SEMS-surgery (n = 105) and SEMS-neoadjuvant-surgery (n = 141). 1:1 propensity score matching (PSM) and 8-week landmark analyses were used to mitigate biases. Primary outcomes included SEMS-related complications, overall survival (OS), and disease-free survival (DFS).Results: In the PSM cohort (n = 206), SEMS-related complication rates were similar between the neoadjuvant and surgery-alone groups (15.5% vs. 14.6%, P = 0.845). The SEMS-neoadjuvant-surgery group demonstrated superior 5-year OS (66.2% vs. 51.7%, P < 0.001) and 5-year DFS (65.3% vs. 40.0%, P < 0.001). Landmark analysis consistently validated these survival benefits. Multivariable Cox regression confirmed neoadjuvant chemotherapy as an independent protective factor for both OS (HR = 0.436, 95% CI: 0.188-0.996, P = 0.015) and DFS (HR = 0.661, 95% CI: 0.551-0.830, P = 0.002).Conclusion: The SEMS-neoadjuvant-surgery strategy is associated with superior long-term survival without increasing SEMS-related complications, strongly supporting its clinical feasibility and oncological safety for COLCC.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079866","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}

引用次数: 0

A prospective observational study of treatment sequencing with regorafenib and FTD/TPI in metastatic colorectal cancer: The OSERO study. 瑞非尼和FTD/TPI治疗转移性结直肠癌的前瞻性观察研究：OSERO研究。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-09-29 DOI: 10.1038/s41416-026-03620-w

Takeshi Kawakami, Toshiki Masuishi, Tetsutaro Hamano, Akihiko Chida, Seiichiro Mitani, Hisateru Yasui, Atsushi Ishiguro, Takayuki Ando, Kentaro Sawada, Kazuaki Harada, Naoki Takahashi, Shogen Boku, Tomomi Kashiwada, Taito Esaki, Ayumu Yoshikawa, Keiji Sugiyama, Kouji Yamamoto, Hironaga Satake, Satoshi Yuki, Kentaro Yamazaki, Eiji Oki

{"title":"A prospective observational study of treatment sequencing with regorafenib and FTD/TPI in metastatic colorectal cancer: The OSERO study.","authors":"Takeshi Kawakami, Toshiki Masuishi, Tetsutaro Hamano, Akihiko Chida, Seiichiro Mitani, Hisateru Yasui, Atsushi Ishiguro, Takayuki Ando, Kentaro Sawada, Kazuaki Harada, Naoki Takahashi, Shogen Boku, Tomomi Kashiwada, Taito Esaki, Ayumu Yoshikawa, Keiji Sugiyama, Kouji Yamamoto, Hironaga Satake, Satoshi Yuki, Kentaro Yamazaki, Eiji Oki","doi":"10.1038/s41416-026-03620-w","DOIUrl":"https://doi.org/10.1038/s41416-026-03620-w","url":null,"abstract":"Background: Regorafenib (REG) monotherapy and trifluridine/tipiracil (FTD/TPI), with or without bevacizumab (BEV), are standard later-line treatments for metastatic colorectal cancer (mCRC). However, the optimal treatment sequence remains uncertain.Methods: The OSERO study was a prospective observational study in patients with mCRC scheduled for later-line treatment with REG or FTD/TPI, with or without BEV (UMIN000040586). Patients were categorized into REG (A), FTD/TPI (B), and FTD/TPI plus BEV (C). The primary endpoint was overall survival (OS). To adjust for imbalances in baseline characteristics, stabilized inverse probability of treatment weights (IPTWs) derived from a propensity score model were applied.Results: Among 468 patients, (A, n = 154; B, n = 82; C, n = 232), scheduled second-line treatment rates were 65.6%, 37.8%, and 62.9%. Median overall survival (mOS) was 12.2, 7.5, and 10.6 months, respectively. After IPTW adjustment, mOS was 12.2 (A) and 10.6 months (C) (hazard ratio, 1.03; 95% confidence interval, 0.81-1.30; P = 0.837). Grade ≥ 3 adverse events ( > 10%) included hand-foot syndrome, proteinuria, and hypertension in (A), and neutropenia and anemia (B, C).Conclusion: Sequential treatment with REGO and FTD/TPI plus BEV therapy yielded comparable survival, suggesting that treatment selection may depend on safety profiles of each drug.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079884","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}

引用次数: 0

VISTA drives tumour-intrinsic proliferation in mesothelioma cells. VISTA驱动间皮瘤细胞的肿瘤内生性增殖。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-09-28 DOI: 10.1038/s41416-026-03639-z

Lisa Kondo-Ida, Tatsuhiro Sato, Emi Mishiro-Sato, Satomi Mukai, Yoshitaka Sekido

{"title":"VISTA drives tumour-intrinsic proliferation in mesothelioma cells.","authors":"Lisa Kondo-Ida, Tatsuhiro Sato, Emi Mishiro-Sato, Satomi Mukai, Yoshitaka Sekido","doi":"10.1038/s41416-026-03639-z","DOIUrl":"https://doi.org/10.1038/s41416-026-03639-z","url":null,"abstract":"Background: Mesothelioma is a therapeutic challenge because current therapies have limited efficacy. In this study, we investigated the role of the immune checkpoint molecule V-domain Ig suppressor of T cell activation (VISTA) in mesothelioma cells.Methods: The effect of VISTA expression on cell proliferation was analysed using mesothelioma cell lines and a mouse xenograft model. To investigate the underlying mechanisms, we performed immunoprecipitation-mass spectrometry and RNA-seq analysis to identify VISTA-associated proteins and downstream transcriptional changes.Results: Analysis of The Cancer Genome Atlas (TCGA) dataset revealed that VISTA and B7-H3 were highly expressed in mesothelioma cells; their expression patterns were positively correlated with those of genes highly expressed in epithelioid and sarcomatoid cells, respectively. Functional studies revealed that VISTA overexpression enhanced proliferation of mesothelioma cell lines, whereas VISTA knockdown markedly suppressed tumour growth in vitro and in vivo. Proteomic profiling revealed interactions between VISTA, cell adhesion molecules and intracellular signalling proteins such as receptor-interacting serine/threonine-protein kinase 1 (RIPK1), whereas RNA sequencing revealed enrichment of TNF signalling, and functional analyses demonstrated enhanced AKT phosphorylation.Conclusions: These findings indicate that VISTA promotes mesothelioma cell proliferation through tumour-intrinsic signalling independent of immune modulation. VISTA is a promising subtype-specific therapeutic target for mesothelioma.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073603","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}

引用次数: 0