Nadeem Al-Khafaji, Frances Steele, Haoxuan Li, Hannah Boyden, Umar Bin Tariq, Joanna Hooper, Adam C Chambers, David E Messenger
{"title":"A comparison of overall survival from early-onset and late-onset colorectal cancer stratified by TNM stage: a systematic review.","authors":"Nadeem Al-Khafaji, Frances Steele, Haoxuan Li, Hannah Boyden, Umar Bin Tariq, Joanna Hooper, Adam C Chambers, David E Messenger","doi":"10.1038/s41416-026-03426-w","DOIUrl":"https://doi.org/10.1038/s41416-026-03426-w","url":null,"abstract":"<p><strong>Background: </strong>There is conflicting evidence whether survival outcomes are better for early-onset colorectal cancer (EOCRC) or late-onset (LO) CRC. This review aimed to determine overall survival (OS) differences between EOCRC and LOCRC stratified by TNM stage.</p><p><strong>Methods: </strong>EMBASE, Ovid MEDLINE and Cochrane Library were searched using approved search terms for CRC, survival outcomes and early onset disease. Studies which compared OS between early- and late-onset CRC, irrespective of age cut-off, stratified by TNM stage, were included. The Methodological Index for Non-randomized Studies was used to assess methodology and risk of bias. Data on 5-year OS, TNM stage, histopathological features, cohort study type and use of confounder-adjusted analyses were extracted and descriptive statistics presented as study heterogeneity prevented meta-analysis.</p><p><strong>Results: </strong>A total of 21 studies described the OS of 332451 patients: 29199 EOCRC and 303252 LOCRC. Studies mostly found favourable outcomes in EOCRC, but where multiple age groups were compared, worse survival was frequently observed in the very youngest patients, especially in stage II and III disease.</p><p><strong>Conclusion: </strong>EOCRC may have worse OS in age and stage subgroups. This warrants further study using large, granular datasets with detailed information on staging and histopathological features. PROSPERO ID CRD42024563472. An earlier version of this review was presented at the Association of Coloproctologists of Great Britain and Ireland Annual General Meeting in July 2023 and the Tripartite Colorectal Meeting 2025.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833467","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}
{"title":"Economic evaluation of artificial intelligence for cancer detection in the UK breast screening programme.","authors":"Harry Hill, Cristina Roadevin","doi":"10.1038/s41416-026-03465-3","DOIUrl":"https://doi.org/10.1038/s41416-026-03465-3","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) offers a potential solution to radiologist shortages in breast cancer screening while maintaining diagnostic accuracy. Retrospective studies suggest AI performs comparably to human readers in detecting cancers, but no economic evaluations have yet used prospective trial data.</p><p><strong>Methods: </strong>We developed a de novo discrete-event simulation model to estimate the cost-effectiveness of integrating AI into the NHS screening pathway using evidence from a large prospective trial.</p><p><strong>Results: </strong>The AI-only strategy generated a small incremental QALY gain of 0.00009 and reduced lifetime costs by £159.55 per woman invited, and had a 100% probability of being most cost-effective at the £20,000/QALY threshold. Replacing one human reader with AI also increased QALYs, by 0.00019, and reduced costs by £31.07. Triple reading (two humans plus AI) produced the largest QALY gain (0.00023) but increased costs by £72.79. All AI-based pathways reduced cancer deaths, shifted cancers from advanced (TNM stage 4) to earlier stages at detection, and increased the proportion of cancers detected by screening.</p><p><strong>Conclusion: </strong>Using AI in place of human readers is likely to be cost-effective, marginally improving health outcomes while reducing overall costs, with full replacement of both human readers being the most cost-effective screening strategy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811235","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}
Roberto Estay, Analía Cortés, Bettina Müller, Fabián Tempio, Consuelo Merino, Camila Fuentes, Andrea Rebolledo, Nicole Ramírez, Patricia Contalba, Karina Bustos, Cristian Pereda, M Alejandra Gleisner, Iván Flores, Fermín E González, Andrés Tittarelli, Adnane Achour, Sofía Hidalgo, Álvaro Lladser, María Inés Becker, Flavio Salazar-Onfray, Mercedes N López
{"title":"Phase I trial of a heat-conditioned tumor lysate vaccine (TRIMELVax) in anti-PD-1 refractory melanoma: safety and immunological aspects (NCT06556004).","authors":"Roberto Estay, Analía Cortés, Bettina Müller, Fabián Tempio, Consuelo Merino, Camila Fuentes, Andrea Rebolledo, Nicole Ramírez, Patricia Contalba, Karina Bustos, Cristian Pereda, M Alejandra Gleisner, Iván Flores, Fermín E González, Andrés Tittarelli, Adnane Achour, Sofía Hidalgo, Álvaro Lladser, María Inés Becker, Flavio Salazar-Onfray, Mercedes N López","doi":"10.1038/s41416-026-03459-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03459-1","url":null,"abstract":"<p><strong>Background: </strong>TRIMELVax is a cancer vaccine prototype derived from heat-conditioned melanoma cell lysates combined with a natural adjuvant. Preclinical studies demonstrated robust antitumor immune responses and tumor regression. We conducted a Phase I clinical trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of TRIMELVax in patients with unresectable stage IV melanoma who had progressed after first-line anti-PD-1 therapy.</p><p><strong>Methods: </strong>Eligible patients had stage IV melanoma with documented progression or unacceptable toxicity following anti-PD-1 treatment. TRIMELVax was administered subcutaneously every four weeks for a total of four doses. The primary endpoints of the study were safety and feasibility, which were assessed according to CTCAE v5.0. Secondary endpoints included efficacy as assessed by RECIST 1.1, overall survival (OS), progression-free survival (PFS), and immunogenicity, evaluated by peripheral blood immune cell responses and delayed-type hypersensitivity (DTH) reactions.</p><p><strong>Results: </strong>Seventeen patients received ≥ 1 dose; 13 completed all four doses. Treatment-related adverse events occurred in 9 patients, with a grade 1 or 2 severity. Two patients experienced manageable grade 3 events. No grade 4-5 toxicities were observed. No complete responses were observed in this cohort. Notably, a partial response was observed in 1 patient, stable disease in 6 patients, yielding a 41% disease control rate; 10 patients progressed. Median OS was 14 months, and median PFS was 5.2 months. DTH positivity was observed in six of the nine patients tested, correlating with the induction of memory T cells in peripheral blood after treatment. Immunomonitoring revealed increased CXCR3 expression in CD8⁺ T cells and decreased CD39 expression in both CD4⁺ and CD8⁺ subsets in patients with disease control. One case with lung metastasis regression exhibited a significant expansion of TCF1⁺PD-1⁺ CD4⁺ and CD8⁺ T cell populations, and an enriched perforin⁺granzyme B⁺ CD8⁺ T cell compartment, consistent with vaccine-associated immune activation.</p><p><strong>Conclusions: </strong>TRIMELVax demonstrated acceptable safety and early signs of clinical activity in anti-PD-1 refractory melanoma patients. These findings support its immunogenic potential and warrant further evaluation in larger, controlled studies.</p><p><strong>Clinicaltrial: </strong>GOV: NCT06556004.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811287","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}
Antonis Valachis, Jürgen Geisler, Peeter Karihtala, Malgorzata K Tuxen
{"title":"Insights on postneoadjuvant treatment among patients with triple-negative breast cancer and residual disease after neoadjuvant therapy: can expert consensus help to interpret the current evidence?","authors":"Antonis Valachis, Jürgen Geisler, Peeter Karihtala, Malgorzata K Tuxen","doi":"10.1038/s41416-026-03452-8","DOIUrl":"https://doi.org/10.1038/s41416-026-03452-8","url":null,"abstract":"<p><p>As treatment strategies for early triple-negative breast cancer continue to evolve, translating clinical evidence into practice can be challenging, especially as the standard of care also shifts and may differ across studies. The management of patients with triple-negative breast cancer who have residual disease after neoadjuvant therapy exemplifies a complex clinical scenario with emerging yet sometimes difficult-to-interpret evidence. Through a critical appraisal of current data and an expert consensus discussion from the Nordic region, the authors present a perspective on postneoadjuvant treatment options for triple-negative breast cancer and discuss potential approaches based on available evidence and expert opinion.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763111","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}
Franziska Springer, Mette Kielsholm Thomsen, Jorne Biccler, Lars Vedel Kessing, Anja Mehnert-Theuerkauf, Annika von Heymann, Christoffer Johansen
{"title":"Incident mental disorders following cancer: analysis of real-world psychiatric outcomes in a nationwide population-based cohort study in Denmark across three decades.","authors":"Franziska Springer, Mette Kielsholm Thomsen, Jorne Biccler, Lars Vedel Kessing, Anja Mehnert-Theuerkauf, Annika von Heymann, Christoffer Johansen","doi":"10.1038/s41416-026-03460-8","DOIUrl":"https://doi.org/10.1038/s41416-026-03460-8","url":null,"abstract":"<p><strong>Background: </strong>Cancer and mental disorders may influence one another, yet research on the risk of developing a new-onset mental disorder following cancer, other than depression, remains limited.</p><p><strong>Methods: </strong>In a nationwide register-based study, patients were followed from incident cancer diagnosis between 1995 and 2015 until end of follow-up 2023, excluding those with preexisting mental disorders. Patients were matched with cancer-free individuals on age, sex, socioeconomic position and comorbidities. We estimated incidence rates (IR) of mental disorders through psychiatric diagnoses and psychotropic medication prescriptions, as well as hazard ratios (HR) in comparison to cancer-free individuals.</p><p><strong>Results: </strong>We included 289,391 cancer patients and 1,031,057 population-matched cancer-free comparisons. Across the cancer cohort, 116,118 developed any incident mental disorder, with a HR of 2.3 [95%-CI: 2.3-2.3] and varying rates across tumor types. IR and HR were highest in the first year after cancer diagnosis and decreased rapidly thereafter, yet the HR remained elevated exceeding ten years. Highest IRs and HRs were observed for anxiety, depression and substance use disorders. Our results were confirmed by several sensitivity analyses.</p><p><strong>Conclusion: </strong>The incidence and risk elevation of incident mental disorders in cancer patients vary based on sex, cancer type, time since diagnosis and type of mental disorder.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763148","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}
Kun Chen, Jianjiao Ni, Yida Li, Sijia Gu, Ye Li, Xi Yang, Shyamal Goswami, Qiyu Luo, Yalei Zhang, Ling Qian, Yudi Hu, Runye Zhou, Yating Wang, Jingjing Liu, Xiuyu Cai, Chunrong Zhang, Saifullah Afridi, Yi Chen, Peng Wang, Zhengfei Zhu
{"title":"Identification of a distinct cluster of LY6E<sup>+</sup> macrophages in esophageal squamous cell carcinoma: functional phenotype, spatial interaction, and prognostic significance.","authors":"Kun Chen, Jianjiao Ni, Yida Li, Sijia Gu, Ye Li, Xi Yang, Shyamal Goswami, Qiyu Luo, Yalei Zhang, Ling Qian, Yudi Hu, Runye Zhou, Yating Wang, Jingjing Liu, Xiuyu Cai, Chunrong Zhang, Saifullah Afridi, Yi Chen, Peng Wang, Zhengfei Zhu","doi":"10.1038/s41416-026-03456-4","DOIUrl":"https://doi.org/10.1038/s41416-026-03456-4","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages are key players in cancer progression, but their heterogeneity is not fully understood. This study aims to investigate the role of a specific macrophage subpopulation marked by LY6E in esophageal squamous cell carcinoma (ESCC).</p><p><strong>Methods: </strong>We analyzed macrophage subsets in ESCC, focusing on LY6E<sup>+</sup> populations. Their gene expression signature, functional characteristics, and correlation with patient prognosis and immunotherapy response were assessed through single cell RNA sequencing and multiplex immunohistochemistry.</p><p><strong>Results: </strong>A distinct LY6E<sup>+</sup> macrophage subpopulation was identified, enriched in tumors and associated with poor prognosis. These cells exhibited an M2-like, immunosuppressive phenotype, yet possessed high phagocytic and antigen-presenting potential. A potential niche involving LY6E<sup>+</sup> macrophages, exhausted CD8<sup>+</sup> T cells, and ICAM2<sup>+</sup> tumor cells was discovered, which predicted a better response to immunotherapy.</p><p><strong>Conclusions: </strong>Our findings reveal a critical and complex role for LY6E<sup>+</sup> macrophages in ESCC, highlighting them as a potential target for therapeutic intervention.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763127","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}
Andrew D Southam, James A Higginson, Gavin R Lloyd, Matthew J Smith, Lauren E Cruchley-Fuge, Rachel Spruce, Ossama Edbali, Ralf J M Weber, Hisham Mehanna, Nikolaos Batis
{"title":"Regional HNSCC metabolomics reveals widespread changes to one-carbon metabolism and S-adenosylmethionine metabolism across tumour core, tumour edge and adjacent non-tumour tissues.","authors":"Andrew D Southam, James A Higginson, Gavin R Lloyd, Matthew J Smith, Lauren E Cruchley-Fuge, Rachel Spruce, Ossama Edbali, Ralf J M Weber, Hisham Mehanna, Nikolaos Batis","doi":"10.1038/s41416-026-03410-4","DOIUrl":"https://doi.org/10.1038/s41416-026-03410-4","url":null,"abstract":"<p><strong>Background: </strong>Cancer, including head and neck squamous cell carcinoma (HNSCC), induces changes to metabolism that drive the disease. Regional metabolomics allows understanding of metabolic variation across the tumour, including in the tumour core, where hypoxia is likely more pronounced.</p><p><strong>Methods: </strong>Ultra-high performance liquid chromatography-mass spectrometry metabolomics was applied to regionally distinct patient tissue samples: tumour edge, tumour core and adjacent non-tumour. Statistical, correlation and pathway enrichment analyses were performed.</p><p><strong>Results: </strong>Markers of hypoxia or pseudohypoxia-lactate, succinate, fumarate, and the lactate:pyruvate ratio-were elevated in both core and edge tumour regions relative to adjacent tissue, with a trend toward stronger changes in the core. One-carbon metabolites were altered in HNSCC, including tumour-associated increases of S-adenosylmethionine (SAM) and SAM metabolites (S-adenosylhomocysteine, polyamines, methylated nucleosides, dimethylarginine, trimethylysine and 1-methylnicotinamide). Histidine, tryptophan, choline and folate appear metabolically connected to one-carbon metabolism in HNSCC: histidine, L-kynurenine (tryptophan metabolite), some purine metabolites (including deoxyguanosine, deoxyinosine) and choline were elevated in tumour tissue; while histidine/SAM, L-kynurenine/deoxyguanosine, L-kynurenine/deoxyinosine and folate/methionine were correlated in tumour tissue only.</p><p><strong>Conclusion: </strong>Tumour edge and core exhibited one-carbon metabolic changes relative to non-tumour, with the magnitude of change generally greater in the core reflecting location dependent variation of SAM metabolism in HNSCC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763186","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}
Chenyu Yang, Yue Ming, Qingbin Wu, Zixia Ye, Yingying Duan, Hulin Ma, Xiaomin Xu, Rong Wei, Xingyang Qiu, Huaping Yang, Yang Yang, Jiawei Guo, Yong Peng
{"title":"SLIRP maintains energy metabolism homeostasis in colorectal cancer by stabilizing mitochondrial-encoded mRNAs.","authors":"Chenyu Yang, Yue Ming, Qingbin Wu, Zixia Ye, Yingying Duan, Hulin Ma, Xiaomin Xu, Rong Wei, Xingyang Qiu, Huaping Yang, Yang Yang, Jiawei Guo, Yong Peng","doi":"10.1038/s41416-026-03453-7","DOIUrl":"https://doi.org/10.1038/s41416-026-03453-7","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a highly vascularised tumour often characterised by elevated oxidative phosphorylation (OXPHOS) activity, positioning OXPHOS as a potential metabolic vulnerability for targeted therapy. SLIRP is an RNA-binding protein involved in the post-transcriptional regulation of mitochondrial gene expression. However, its specific function and underlying mechanism in CRC remain poorly understood.</p><p><strong>Methods: </strong>Clinical specimens and public databases were utilised to analyse both the subcellular localisation and expression of SLIRP in CRC. The functional role of SLIRP in CRC progression was assessed through cell growth, apoptosis, and metabolic analyses. Post-transcriptional regulation of mitochondrial-encoded mRNAs by SLIRP was investigated using RNA immunoprecipitation and mRNA stability assays.</p><p><strong>Results: </strong>SLIRP expression was significantly elevated in CRC tissues compared to adjacent normal tissues, and high SLIRP expression correlated with poor patient survival. SLIRP knockdown induced an ATP crisis, leading to suppressed tumour growth and increased apoptosis in CRC cells. Mechanistically, SLIRP globally binds to mitochondrial-encoded mRNAs and maintains their stability, functioning as a key post-transcriptional regulator of mitochondrial gene expression.</p><p><strong>Conclusions: </strong>These findings uncover a critical role for SLIRP in maintaining OXPHOS activity in CRC and highlight its potential as both a prognostic biomarker and a therapeutic metabolic target.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763228","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}
{"title":"Lethal clinical outcome and immune desert contexture in refractory gastric cancer harboring CCNE1 amplification and overexpression.","authors":"Yun Gu, Jieti Wang, Zhen Ling, Jingquan Liu, Chao Lin, Hao Liu, Hongyong He, Ruochen Li, Shao Fei, Jiejie Xu","doi":"10.1038/s41416-026-03461-7","DOIUrl":"https://doi.org/10.1038/s41416-026-03461-7","url":null,"abstract":"<p><strong>Background: </strong>The epithelial-mesenchymal axis frames gastric cancer heterogeneity but mainly captures phenotypic extremes. CCNE1 gain, encompassing amplification or Cyclin E1 overexpression, represents one intermediate state linked to chromosomal instability and therapeutic resistance. However, its clinicopathologic identity and immune features in gastric cancer remain insufficiently characterised.</p><p><strong>Methods: </strong>We analysed 1273 gastric cancer patients across six independent cohorts: ZSHS (n = 453), TCGA (n = 410), ACRG (n = 300), SMC (n = 43), MSKCC (n = 22), and ZSHS NGS cohort (n = 45). Tumours were classified into CCNE1 gain, epithelial, or mesenchymal subtypes using protein, copy-number, or transcript-level data. Clinicopathologic features, survival outcomes, treatment responses, and immune contexture were evaluated across subtypes.</p><p><strong>Results: </strong>CCNE1 gain tumours retained E-cadherin positivity but showed increased proliferation, more nerve and venous invasion. They were associated with poor prognosis and reduced response to adjuvant chemotherapy, HER2-targeted therapy, anti-angiogenic agents, and PD-1 blockade independent of epithelial-mesenchymal classification. The immune contexture exhibited an immune-desert phenotype with reduced lymphocyte infiltration, impaired cytotoxicity, increased M2 macrophage polarisation, and elevated TGF-β.</p><p><strong>Conclusion: </strong>CCNE1 gain delineates a clinic-ready, therapy-refractory subtype of gastric cancer beyond the epithelial-mesenchymal framework, representing over one in ten patients. These tumours preserve epithelial morphology yet exhibit aggressive proliferative and invasive behaviour, coupled with immune desert and myeloid-driven suppression.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763122","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}
Angelica Rigutto, Nicolás G Núñez, Jenny C Kienzler, Isabelle Opitz, Mayura Meerang, Martina Haberecker, Nadine Fournier, Joao Lourenço, Raphael Gottardo, Karina Silina, Anurag Gupta, Burkhard Becher, Alessandra Curioni-Fontecedro
{"title":"Multiplexed single-cell and spatial profiling reveal B cells and tertiary lymphoid structures as prognostic indicators in pleural mesothelioma.","authors":"Angelica Rigutto, Nicolás G Núñez, Jenny C Kienzler, Isabelle Opitz, Mayura Meerang, Martina Haberecker, Nadine Fournier, Joao Lourenço, Raphael Gottardo, Karina Silina, Anurag Gupta, Burkhard Becher, Alessandra Curioni-Fontecedro","doi":"10.1038/s41416-026-03421-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03421-1","url":null,"abstract":"<p><strong>Background: </strong>Pleural mesothelioma (PM) is an orphan disease with poor prognosis. While T cell dynamics in the tumor microenvironment (TME) have been extensively studied, the role of B cells remains poorly characterized. Tumor-infiltrating B cells, particularly when organized into tertiary lymphoid structures (TLS), have been associated with improved outcomes of patients with cancer.</p><p><strong>Methods: </strong>In this study, high-dimensional flow cytometry (HDCyto) and high-plex imaging were applied to analyze fresh-frozen and formalin-fixed paraffin-embedded (FFPE) PM tumor samples, enabling a comprehensive immune profiling of the TME.</p><p><strong>Results: </strong>We identified 15 distinct immune cell subsets and stratified tumors into three subgroups with significantly different survival outcomes. Longer survival correlated with increased T and B cell infiltration, with B cells and CD4+ T cells forming TLS in specific cases.</p><p><strong>Conclusions: </strong>These findings underscore the heterogeneity of PM tumors and highlight the critical role of B cells and TLS in shaping anti-tumor immunity and influencing patient prognosis.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763155","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}