British Journal of Cancer最新文献

{"title":"CXCL14+ fibroblasts promote development of IBD-associated fibrosis and cancer by interacting with SPP1+ macrophages via collagen IV secretion.","authors":"Haonan Zhang, Yulu Shi, Qiuyu Song, Na Li, Zhaoxian Lin, Qiusan Chen, Yi Yang, Yanjun Chen, Qian Liu, Yan Tan, Yifeng Zheng, Shanping Wang, Yan Sun, Xiaxi Li, Chengcheng He, Lanxiang Zhu, Mingsong Li","doi":"10.1038/s41416-026-03636-2","DOIUrl":"https://doi.org/10.1038/s41416-026-03636-2","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of inflammatory bowel disease (IBD) involves chronic inflammation of the gastrointestinal tract, which predisposes patients to an increased risk of fibrosis and cancer due to prolonged inflammatory stimulation. However, the specific mechanisms underlying secondary gastrointestinal carcinogenesis in individuals with IBD remain poorly elucidated, particularly due to a limited number of studies conducted at single-nuclei level.</p><p><strong>Methods: </strong>We investigated the dynamics and interactions of cell subtypes during the progression of IBD-associated cancers through comprehensive analysis including single-nuclei transcriptomics, spatial transcriptomics, ecological dynamic modelling, multiplex immunohistochemistry, in vitro co-culture and in vivo animal studies.</p><p><strong>Results: </strong>The results revealed that CXCL14+ fibroblasts, the primary source of collagen in the microenvironment, play a pivotal role in the inflammation-cancer transition. These fibroblasts progressively increase in abundance during this transition and secreted elevated levels of collagen IV. The increased presence of collagen IV promotes the recruitment and differentiation of SPP1+ macrophages. This interaction ultimately contributes to the development and progression of IBD-associated fibrosis and cancer transformation. Collagen IV, secreted by CXCL14+ fibroblasts, plays a pivotal role in promoting the transition from IBD to cancer. Inhibition of collagen IV secretion not only prevents fibrosis but also hinders the development of inflammation-cancer transition.</p><p><strong>Conclusion: </strong>Our findings are crucial for understanding the mechanisms underlying IBD-associated cancer and developing innovative therapeutic strategies. During the inflammation-cancer transition, activation of the SOX4 leads to increased COL4A1/A2 secretion by CXCL14+ fibroblasts, resulting in enhanced collagen IV synthesis. Collagen IV binds to ITGB1/CD44 receptors on SPP1+ macrophages and activates EGR1/2 to promote SPP1+ macrophage differentiation, while upregulating S100A10 and ANXA2. Activation of S100A10 and ANXA2 promotes recruitment of SPP1+ macrophages, which contributes to immune escape and secretion of oncogenes, thus further promoting fibrosis and tumorigenesis. In addition, SPP1+ macrophages further stimulate CXCL14+ fibroblasts to secrete COL4A1/A2 via TGF-β1, forming a feedback loop that amplifies interactions in the tumour microenvironment.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214964","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":"Waiting times and determinants of delay for head and neck cancer in England-a population cohort study using real world data.","authors":"Farizeh Jashek-Ahmed, Orouba Almilaji, Thomas E Cowling, David W Hamilton, Kate Walker, Vinidh Paleri","doi":"10.1038/s41416-026-03630-8","DOIUrl":"https://doi.org/10.1038/s41416-026-03630-8","url":null,"abstract":"<p><strong>Background: </strong>In Head and Neck Cancer (HNC), even short delays in treatment can worsen prognosis. We used real-world data to quantify waiting times and identify patient, tumour and health service factors associated with treatment delay in England.</p><p><strong>Methods: </strong>Using linked national datasets (Cancer Registry, Cancer Waiting Times, Hospital Episodes Statistics, Radiotherapy and Chemotherapy), we calculated waiting times from referral to first treatment (surgery or (chemo)radiation) and used multivariable logistic regression models to examine factors associated with delay.</p><p><strong>Results: </strong>Of 30,506 patients, 43% experienced treatment delay ( > 62 days from referral). Long delays ( > 90 days) affected 11% of patients treated with primary surgery and 20% of those receiving primary (chemo)radiation. Non-urgent referral (30% of patients) was the strongest predictor of long delay (aOR 4.07, CI: 3.54-4.68). Additional risk-factors included initial assessment at non-specialist (spoke) hospitals, non-oropharyngeal cancers, and higher socio-economic deprivation.</p><p><strong>Conclusions: </strong>Treatment delays in HNC are worsening, particularly for patients treated with primary (chemo)radiation. Referral route is the strongest determinant. Interventions should focus on optimising referral pathways, increasing awareness of HNC symptoms among the public and primary care, and acknowledging the different drivers of delay associated with surgery and (chemo)radiation therapy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206436","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":"Preclinical efficacy of a systemically-administered, second-generation STING agonist that promotes anti-tumour immunity in combination with radiotherapy.","authors":"Malin Pedersen, Lisa C Hubbard, Shane Foo, Anton Patrikeev, Antonio Rullan, Holly Baldock, Christian Mandl, Paolo Chetta, Jehanne Hassan, Isaac Dean, Naomi Guppy, Philippe Slos, Charleen Chan Wah Hak, Elizabeth Appleton, Emmanuel C Patin, Rachel Hunt, Justin Weir, Masahiro Ono, Thorsten Oost, Ulrich Reiser, Thomas Zichner, Kevin Morse, Mary Murphy, Lingqi Luo, Reniqua House, Louise Giffin, Alan A Melcher, Anne Vogt, Sebastian Carotta, Kevin J Harrington","doi":"10.1038/s41416-026-03634-4","DOIUrl":"https://doi.org/10.1038/s41416-026-03634-4","url":null,"abstract":"<p><strong>Background: </strong>As potent triggers of innate immunity, STING agonists hold promise as active immunotherapeutic agents for cancer treatment. Second-generation STING agonists, suitable for systemic delivery, are being investigated in preclinical research and have entered clinical trials. Here, the novel synthetic STING agonist, BI-1703880 (STINGa), was investigated for anti-tumour and immunological effects.</p><p><strong>Methods: </strong>We used human and murine immune and tumour cells to examine the effects of STINGa in vitro, and preclinical cancer mouse models to investigate effects in vivo.</p><p><strong>Results: </strong>We show that STINGa activates the STING pathway and results in a transient and dose-dependent upregulation and secretion of interferons and proinflammatory cytokines in vitro and in vivo. We show that intravenous administration of repeated dosing with low-dose STINGa is well tolerated. We report that radiotherapy (RT) and STING agonism synergises to generate innate immune cell and CD8+ T cell responses that control tumour growth. RT/STINGa upregulated PD-L1, PD-1 and CTLA-4 in the tumour microenvironment. Our findings show that combining RT/STINGa with immune checkpoint inhibitors further increases therapeutic benefit.</p><p><strong>Conclusions: </strong>Our data confirm STING as a therapeutic target in cancer and support the clinical development of BI1703880 STING agonist, thereby suggesting radiotherapy as a potential combination for enhancing anti-tumour efficacy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191209","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":"Retraction Note: Chromatin structure, transcriptional activity and DNA repair efficiency affect the outcome of chemotherapy in multiple myeloma.","authors":"M Gkotzamanidou, P P Sfikakis, S A Kyrtopoulos, C Bamia, M A Dimopoulos, V L Souliotis","doi":"10.1038/s41416-026-03646-0","DOIUrl":"https://doi.org/10.1038/s41416-026-03646-0","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191269","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":"Paediatric therapeutic development workshop on desmoplastic small round cell tumours.","authors":"Joseph S Baxter, Jan J Molenaar, Arushi Agrawal, Ana Teresa Amaral, Patricia Blanc, Nikki Bowdidge, Richard Bowdidge, Bernadette Brennan, Michela Casanova, David da Silva Moura, Sam Daems, Laura Danielson, Solomon English, Patrick Grohar, Emma Halliwell, Paul Huang, Pamela Kearns, Christopher A Klebanoff, Konstantinos Klaourakis, Marc Ladanyi, Geffen Lass, Katerina Lawlor, Corinne M Linardic, Joseph Ludwig, Stella Man, Leo Mascarenhas, Lucy Metayer, Michael Torsten Meister, Veronique Minard-Colin, Siwan Oldham, Daniel Orbach, Sheena Patel, Sandro Pasquali, Reineke A Schoot, Rob Sellar, Janet Shipley, Monika Sparber-Sauer, Silvia Stacchiotti, William Tap, Giovana Tardin Torrezan, Danh D Truong, Marc van de Wetering, Madina Wane, Joshua J Waterfall, Aaron Weiss, Janet Vasquez-Campbell, Andrew Dj Pearson, David Jenkinson, Andrea Ferrari, Sophie Postel-Vinay, Emily Slotkin","doi":"10.1038/s41416-026-03631-7","DOIUrl":"https://doi.org/10.1038/s41416-026-03631-7","url":null,"abstract":"<p><p>The sixth Paediatric Therapeutic Development Workshop focused on desmoplastic small round cell tumours (DSRCT). Less than 20% of patients with DSRCT survive beyond 5 years and there is no targeted therapy for this disease, which represents an urgent unmet need for new therapeutics. High priority targets include the EWSR1::WT1 fusion protein, the oncogenic driver, and targeting a junction-derived neopeptide presented by HLA-A*03 and HLA-A*11 using a T-cell receptor (TCR) is a novel approach. Other targets (LRRC15, SSTR3 and SSTR5, NECTIN4, STEAP1 and mesothelin) require further validation. Targeting ERBB2/HER2 or claudin-6 by antibody-drug conjugates (ADCs) and NTRK3 by a small molecule inhibitor are promising approaches and are currently being evaluated. Existing clinical assets targeting (in order of importance) B7-H3, the DNA damage response, androgen signalling, FGFR4 and STEAP1 are also high priorities for evaluation in DSRCT, but obtaining therapeutics for clinical trials is a barrier. In view of the rarity of DSRCT, a global initiative in preclinical and clinical research to establish international trials and collect data from patients treated in a harmonised form would benefit patients. Progress can be made by a combined approach of developing new agents whilst evaluating existing therapeutics in well-designed trials.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179603","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":"Using the Geriatric Core Dataset (G-CODE) to predict mortality in older patients with cancer: development and external validation.","authors":"Anne-Laure Couderc, Claudia Martinez-Tapia, Simone Mathoulin-Pelissier, Marie Laurent, Michael Bringuier, Pierre Gay, Philippe Caillet, Jeanne Bertona, Laurent Greillier, Johanna Canovas, Pierre Soubeyran, Siri Rostoft, Florence Canouï-Poitrine, Elena Paillaud","doi":"10.1038/s41416-026-03641-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03641-5","url":null,"abstract":"<p><strong>Background: </strong>The Geriatric Core Dataset (G-CODE) was developed to standardise geriatric assessment (GA) in older adults with cancer. This study aimed to develop and externally validate a mortality prediction score based on the G-CODE at 6-month (main endpoint), 12- and 24-month (secondary endpoints), in older patients with cancer.</p><p><strong>Methods: </strong>Data came from two prospective French cohorts of cancer patients aged ≥70 referred for GA: the Elderly Cancer Patients (ELCAPA) cohort (training set) and the Geriatric Oncology Marseille (GOM) cohort (validation set). G-CODE items were evaluated using multivariate Cox regression analyses, with Akaike information criterion selection. Discrimination was assessed using time-dependent area under the receiver operator curve (tAUC) for 6-, 12-, and 24-month mortality.</p><p><strong>Results: </strong>We included 950 and 766 patients in the training and validation sets (mean ± sd age: 83 ± 6 years/81 ± 6 years; men: 55%/59%; 6-month mortality: 27%/22%). The final G-CODE model highlighted five strong predictors of 6-month mortality: not having a caregiver, weight loss, comorbidities, an impaired 4-instrumental activities of daily living score, and an impaired timed-up-and-go test. The tAUCs of the model, including the G-CODE, age, cancer type, metastases, and treatment, were 82%, 78% and 80%.</p><p><strong>Conclusions: </strong>The final G-CODE score (range: 0-17) accurately predicts 6-, 12-, and 24-month mortality.</p><p><strong>Clinical trial registration: </strong>NCT02884375 (ClinicalTrials.gov).</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165347","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":"Hypoxia-induced HMGB1/NLRP3/Caspase-1 signaling axis enhances proliferation of oral squamous cell carcinoma.","authors":"Kaixiang Wu, Shupeng Zhang, Lu Cao, Jun Wang, Minghui Wang, Zhiwei Zheng, Xiaodong Feng","doi":"10.1038/s41416-026-03632-6","DOIUrl":"https://doi.org/10.1038/s41416-026-03632-6","url":null,"abstract":"<p><strong>Background: </strong>The hypoxic microenvironment, a common feature of solid tumors, is critically involved in driving cancer malignancy. This research focuses on elucidating the function of high mobility group box 1 (HMGB1), induced by such hypoxia, in the context of oral squamous cell carcinoma (OSCC).</p><p><strong>Methods: </strong>We first profiled HMGB1 expression patterns in clinical OSCC specimens and evaluated their potential associations with clinicopathological parameters. To functionally characterize HMGB1, we conducted in vitro experiments utilizing silencing strategies. The impact of chronic cyclic hypoxia and HMGB1 depletion on key cellular processes-including proliferation, pyroptosis, and cell cycle-was systematically examined in OSCC cells. Signaling activity along the HMGB1/NLRP3/Caspase-1 axis was determined by immunoblotting. Furthermore, in vivo relevance was substantiated through murine xenograft models and a 4-NQO-induced carcinogenesis protocol.</p><p><strong>Results: </strong>Analysis of clinical samples revealed that HMGB1 is constitutively upregulated in OSCC tissues. This elevated expression demonstrated a positive relationship with both increased tumor dimensions and lymph node metastasis. Subsequent Kaplan-Meier survival curves indicated that heightened HMGB1 levels are a marker for unfavorable patient outcomes. Furthermore, in cell culture systems, hypoxia treatment significantly elevates HMGB1 expression levels in OSCC cells. Knockdown of HMGB1 expression inhibits hypoxia-induced NLRP3, cleaved-caspase-1, and HIF-1α expression. Hypoxia treatment markedly enhanced OSCC cell proliferation, induced pyroptosis, and alleviated G2/M phase arrest, while HMGB1 knockdown reversed the pro-tumor effects of hypoxia. In vivo experiments demonstrated that HMGB1 knockdown inhibited tumor growth, whereas NLRP3 or caspase-1 deficiency delayed oral cancer progression.</p><p><strong>Conclusion: </strong>Our findings suggested that HMGB1 contributes to the progression of OSCC and has prognostic value. Targeting the hypoxia-induced HMGB1/NLRP3/Caspase-1 signaling axis may offer a viable therapeutic strategy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164602","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":"LAIR1 suppresses phagocytosis via SHP2/USP22-mediated MYH9 degradation in glioma-associated microglia/macrophages to drive immunosuppression.","authors":"Zirui Wang, Qifan Sun, Chunzhao Li, Tai Sun, Zhongning He, Yi Wang, Ruijie Li, Xiukun Lin, Miriam Galvonas Jasiulionis, Nan Ji, Yang Zhang, Huanli Xu","doi":"10.1038/s41416-026-03617-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03617-5","url":null,"abstract":"<p><strong>Background: </strong>Glioma immunotherapy faces major challenges due to the pervasive presence of glioma-associated microglia/macrophages (GAMs) and inadequate T-cell responses. LAIR1 is highly expressed in GAMs and correlates with poor glioma prognosis. This study investigated its role in GAMs and immunosuppression in glioma.</p><p><strong>Methods: </strong>LAIR1 expression was analysed via bioinformatics, flow cytometry, and multiplex immunohistochemical staining. Its function was studied using Lair1^-/- mice, engineered BV2 cells, bone marrow-derived macrophages (BMDMs), patient-derived GAMs, and techniques including RNA-seq, PCR array, co-immunoprecipitation, molecular dynamics analysis, and CRISPR/Cas9.</p><p><strong>Results: </strong>LAIR1 was predominantly expressed on GAMs, and high infiltration of LAIR1^high GAMs correlated with poor patient survival. In orthotopic glioma models, LAIR1 deficiency reduced tumour burden. LAIR1^high GAMs exhibited an immunosuppressive phenotype, associated with the CD47-SIRPA axis. These GAMs conferred resistance to anti-PD-1 therapy. LAIR1 deficiency enhanced GAM tumoricidal activity in vitro. Mechanistically, collagen I-activated LAIR1 promoted SHP2-dependent dephosphorylation of MYH9 at Ser1943. This inhibited USP22 recruitment, blocking USP22-mediated deubiquitylation and stabilisation of MYH9 and HIF1α, ultimately suppressing GAM phagocytosis.</p><p><strong>Conclusion: </strong>LAIR1 is a critical phagocytosis suppressor in GAMs, driving glioma immunosuppression. Targeting LAIR1 represents a promising strategy to restore anti-tumour immunity.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135246","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":"Trends in incidence and prevalence of patients living long-term with de novo metastatic incurable cancer: a retrospective cohort study.","authors":"Ruben Bouma, Olaf P Geerse, Natasja J H Raijmakers, Heidi P Fransen, Lia van Zuylen, Anna K L Reyners, Kristel van Asselt, Maatje D A van Gastel, Daan Brandenbarg, Mariken E Stegmann","doi":"10.1038/s41416-026-03627-3","DOIUrl":"https://doi.org/10.1038/s41416-026-03627-3","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic advances have improved the survival of incurable cancer patients, creating a growing population living long-term with incurable cancer. However, little is known about their epidemiological characteristics. We aimed to examine trends in annual incidence and prevalence among patients living long-term with de novo metastatic incurable cancer in the Netherlands and to describe additional relevant sociodemographic and clinical characteristics among patients diagnosed in recent years.</p><p><strong>Methods: </strong>A population-based, retrospective cohort study using data from the Netherlands Cancer Registry was performed. Adults (≥18 years) diagnosed with de novo metastatic solid tumors in 2000-2021 who survived ≥2 years after their diagnosis were included. Annual incidence, prevalence, key demographic, and tumor characteristics were calculated.</p><p><strong>Results: </strong>Annual incident cases of patients living long-term with de novo metastatic incurable cancer increased from 1298 (2000) to 5398 (2021), representing 12.0-22.6% of incurable cancer diagnoses. In February 2024, at least 18,466 patients in the Netherlands were living long-term with de novo metastatic incurable cancer (1 per 1000 inhabitants). Mean age was 64 years (SD 12), 59.4% were male, and 55.8% (n = 10,310) were alive 2- < 5 years after diagnosis, 31.0% (n = 5721) 5- < 10 years, and 13.2% (n = 2435) ≥ 10 years. The most common tumor types were prostate (35.6%), lung (20.2%), breast (14.4%), and colorectal cancer (6.3%).</p><p><strong>Conclusion: </strong>Substantial increases in the incidence and prevalence were identified, reflecting a shift toward prolonged survival within the incurable cancer population. Greater awareness and research are needed to inform care for this emerging group.</p>","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":"149104308","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":"Integrated spatial and single-cell transcriptomics uncover IFI6⁺ regulatory T-cells and SPP1⁺ macrophages immunosuppressive niches in colorectal cancer.","authors":"Dominika Miroszewska, Shiyang Song, Víctor Urbiola-Salvador, Mariana Cázares Olivera, Agnieszka Jabłońska, Marika Bolcewicz, Leszek Kalinowski, Katarzyna Duzowska, Kinga Drężek-Chyła, Marek Zdrenka, Ewa Śrutek, Łukasz Szylberg, Michał Jankowski, Dariusz Bała, Wojciech Zegarski, Tomasz Nowikiewicz, Natalia Filipowicz, Arkadiusz Piotrowski, Jan P Dumanski, Bin Li, Zhi Chen","doi":"10.1038/s41416-026-03637-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03637-1","url":null,"abstract":"<p><strong>Background: </strong>In colorectal cancer (CRC), tumor-immune interactions are critical drivers of tumorigenesis, immune evasion, and therapeutic response. Therefore, a deeper spatially resolved understanding of these interactions is urgently needed.</p><p><strong>Methods: </strong>Spatial transcriptomics (ST) of CRC and matched normal samples was used to characterize cell populations and gene expression patterns associated with tumorigenesis and immune infiltration. An additional 41 publicly available ST slides, single-cell transcriptomics and bulk transcriptomics datasets from 472 and 617 CRC patients, respectively, were analyzed to validate the findings.</p><p><strong>Results: </strong>Cancer regions exhibited profound molecular alterations with increased oncogenic pathways, immunosuppressors, and tryptophan deprivation via KYNU-AHR axis, inducing the macrophage attractant CXCL5, contributing to immune evasion. In tumor boundaries, SPP1⁺ macrophages fostered an immunosuppressive microenvironment with regulatory T-cells (Tregs) recruited via CCL18-CCR8 and CCL22-CCR4. SIT1 emerged as a potential anti-tumor T-cells suppressor within tertiary lymphoid structures, suggesting a novel immune regulator. We also uncovered a previously uncharacterized population of tumor-infiltrating IFI6⁺ Tregs associated with unfavorable prognosis and therapy response, defined by elevated interferon-related genes and LGALS9, a potential immune checkpoint target.</p><p><strong>Conclusion: </strong>This study uncovered previously unrecognized immunosuppressive cell populations and key immune regulators that advance understanding of CRC immune evasion and highlight potential targets for personalized immunotherapy.</p>","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":"149104289","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}