Nature cancer最新文献

{"title":"Commensal Nakaseomyces glabratus migrates into prostate tumors to accelerate cancer progression","authors":"Ping Lai, Lei Liu, Nicolò Pernigoni, Yingxi Du, Daniele Braga, Martina Troiani, Giuseppe Attanasio, Yuxin Li, Pan Song, Emiliano Pasquini, Tanja Rezzonico Jost, Xiaowen Huang, Martino Maddalena, Simone Mosole, Andrea Rinaldi, Giovanna Pecoraro, Martino Pedrani, Aurora Valdata, Nicolò Bancaro, Luisa Maraccani, Alessandra De Giani, Wei Yuan, Lewis Gallagher, Khobe Chandran, Penny Flohr, Pasquale Rescigno, Giuseppe Reitano, Alessandro Morlacco, Fabrizio Dal Moro, Isabella Giacomini, Monica Montopoli, Matteo Brunelli, Serena Pedron, Ricardo Pereira Mestre, Raad Z. Gharaibeh, Christian Jobin, Silke Gillessen Sommer, Johann de Bono, Andrea Alimonti","doi":"10.1038/s43018-026-01229-9","DOIUrl":"10.1038/s43018-026-01229-9","url":null,"abstract":"Recent studies demonstrate that the gut mycobiota plays a key role in several tumors. However, the contribution of commensal fungi to prostate cancer initiation and progression remains understudied. Here we find that Nakaseomyces glabratus is enriched in fecal, blood and tumor samples of patients with castration-resistant prostate cancer, correlating with patients’ poor overall survival. Oral administration of N. glabratus to castrated mice accelerated cancer progression by promoting infiltration and activation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, androgen deprivation therapy increases intestinal permeability, resulting in the leakage of N. glabratus from the gut to the tumor site, activating PMN-MDSCs via the Dectin-2 receptor. Treatment of mice with a negatively charged intestinal hydrogel blocks N. glabratus translocation to tumor, reducing PMN-MDSCs’ intratumoral infiltration and activation. Taken together, these findings reveal that the gut-to-tumor translocation of N. glabratus contributes to endocrine resistance in prostate cancer by enhancing the immunosuppressive microenvironment of these tumors. Lai et al. show that Nakaseomyces glabratus is enriched in fecal and tumor samples of patients with castration-resistant prostate cancer and that administration of the fungus accelerates cancer progression in prostate cancer-bearing castrated mice.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 10","pages":"1592-1609"},"PeriodicalIF":28.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01229-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SlideChat is a multimodal generative artificial intelligence assistant for whole-slide computational pathology across cancer types","authors":"Ying Chen, Chenglong Ma, Qiongqiong Li, Fang Yan, Yirong Chen, Tianbin Li, Jin Ye, Ming Hu, Yuxiang Lin, Yanjun Li, Guoan Wang, Huihui Xu, Hui Dong, Xiang Wang, Xiaoxiao Xu, Yanyan Zhou, Xia Zhu, Sen Yang, Xiyue Wang, Lu Zhang, Yu Qiao, Rongshan Yu, Junjun He, Yuanfeng Ji","doi":"10.1038/s43018-026-01220-4","DOIUrl":"10.1038/s43018-026-01220-4","url":null,"abstract":"Multimodal artificial intelligence, albeit showing great potential in computational pathology, remains limited to isolated patch-level interpretation and often fails to analyze gigapixel-scale whole-slide images (WSIs) essential for clinical utility. Here we present SlideChat, a multimodal generative artificial intelligence assistant for whole-slide computational pathology across cancer types. SlideChat integrates patch-level and slide-level pathology encoders with a pretrained large language model. Using 274,233 multimodal instruction samples, SlideChat is trained to learn the associations between WSIs and diagnostic reports and interpret complex queries in clinical practice. Evaluated on 8,836 closed-ended questions, 129 open-ended questions and 3,149 WSI reports from five cohorts spanning 31 cancer types, SlideChat outperformed leading baselines by 19.1% in closed-ended accuracy and by 7.7% in report-generation Metric for Evaluation of Translation with Explicit Ordering score and received the highest expert ratings across five dimensions in open-ended question answering, showing the potential to enhance diagnostic workflows, medical education and clinical decision-making. Chen et al. have developed SlideChat, a multimodal generative artificial intelligence assistant, which they benchmark on 27 pathology tasks across 33 cancer types. Expert pathologists rated the assistant as clinically relevant and accurate.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1454-1468"},"PeriodicalIF":28.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874800","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":"l-Glutamine’s potential to enhance chemotherapy efficacy in advanced pancreatic cancer","authors":"","doi":"10.1038/s43018-026-01231-1","DOIUrl":"10.1038/s43018-026-01231-1","url":null,"abstract":"The addition of oral l-glutamine to first-line gemcitabine plus nab-paclitaxel appears safe and is associated with improved survival outcomes and tumor responses compared with historical benchmarks in untreated advanced pancreatic cancer. The beneficial effects of l-glutamine may be mediated through modulation of intermediary metabolism, gut microbial function, inflammatory responses and gut barrier integrity.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1328-1329"},"PeriodicalIF":28.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874797","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":"Publisher Correction: Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial","authors":"Elizabeth A. R. Garfinkle, Renzo Perales-Linares, Ryan C. Gimple, Alexandra J. Livingstone, Kaleigh F. Roberts, Omar H. Butt, S. Peter Goedegebuure, Michael D. McLellan, Gue Su Chang, Jasreet Hundal, Jian Yan, Jaye B. Navarro, Sophia A. Paxton, Srestha Chattopadhyay, Neil Cooch, Alfredo Perales-Puchalt, Konstantina Stavroulaki, Sarah Rochestie, Joann Peters, Beth Junker, Jian L. Campian, Milan G. Chheda, Michael R. Chicoine, Albert H. Kim, Jon T. Willie, Gregory J. Zipfel, Joshua L. Dowling, Christopher A. Miller, Obi L. Griffith, Malachi Griffith, William E. Gillanders, Katherine E. Miller, Elaine R. Mardis, Niranjan Y. Sardesai, Gavin P. Dunn, Tanner M. Johanns","doi":"10.1038/s43018-026-01243-x","DOIUrl":"10.1038/s43018-026-01243-x","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1469-1469"},"PeriodicalIF":28.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01243-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"l-Glutamine in combination with first-line gemcitabine and nab-paclitaxel in advanced pancreatic ductal adenocarcinoma: an open-label, single-arm, phase 1 GlutaPanc trial","authors":"Jun Gong, Hayato Muranaka, So Yung Choi, Mourad Tighiouart, Shrikant Bhute, Ezinne R. Aja, Jonathan P. Jacobs, Aleksandr Stotland, Jennifer Van Eyk, Omer H. M. Elmadbouh, Mouad Edderkaoui, Sunao Tanaka, Hideki Furuya, Arsen Osipov, Jeremy Lorber, Sandrine Billet, Alexzandra Morris, Johanna ten Hoeve-Scott, Thomas Graeber, Stephen J. Pandol, Andrew Hendifar, Neil A. Bhowmick","doi":"10.1038/s43018-026-01225-z","DOIUrl":"10.1038/s43018-026-01225-z","url":null,"abstract":"Exogenous l-glutamine has preclinical antitumor activity although formal clinical translation has not been attempted. We conducted a single-arm phase 1 trial to assess the safety and preliminary efficacy of clinical-grade, US Food and Drug Administration-approved l-glutamine therapy with gemcitabine and nab-paclitaxel (GA) in participants with treatment-naive, advanced pancreatic cancer (n = 16). The primary endpoint was to determine the recommended phase 2 dose (RP2D) by adaptive Bayesian design across standard doses of GA and a dose range of 0.1–0.3 g kg−1 twice-daily oral l-glutamine. Secondary endpoints included safety and preliminary efficacy of the study combination. The primary endpoint was met with the RP2D reached at maximum doses of l-glutamine and GA. The grade ≥3 treatment-related adverse event rate was 66.7%, primarily from GA. Addition of l-glutamine to GA induced tumor shrinkage in 94% of subjects with a best overall response rate (ORR) of 44% (12.5% complete response). Median progression-free survival and overall survival (OS) were 8.5 months (95% confidence interval (CI) 6–not reached (NR)) and 22 months (95% CI 11–NR), respectively. l-Glutamine induced distinct metagenomic and metabolomic signatures on exploratory analyses in glutamine-treated subjects as a single agent, while the combination of l-glutamine and GA nearly doubled the ORR and tripled the OS compared to historical GA alone (ClinicalTrials.gov registration: NCT04634539 ). In this open-label, single-arm, phase 1 GlutaPanc trial, Gong and colleagues report the safety and feasibility of l-glutamine in participants with advanced pancreatic ductal adenocarcinoma and determine the recommended phase 2 dose of l-glutamine in combination with gemcitabine and nab-paclitaxel.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1406-1418"},"PeriodicalIF":28.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01225-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galanin impairs tumor immunity in glioblastoma by promoting infiltration and ferroptosis resistance of myeloid-derived suppressor cells","authors":"Lizhi Pang, Yang Liu, Fei Zhou, Songlin Guo, Fatima Khan, Heba Ali, Hardik Shah, Sara Huber, Barbara Kofler, Craig M. Horbinski, Peiwen Chen","doi":"10.1038/s43018-026-01221-3","DOIUrl":"10.1038/s43018-026-01221-3","url":null,"abstract":"Glioblastoma (GBM) is a highly aggressive and lethal form of brain tumor that resists immunotherapy. Here we show that neuropeptide galanin (GAL) drives immunosuppression and immunotherapy resistance in GBM. Mechanistically, GBM cell-secreted GAL interacts with its receptor GALR3 on monocytic myeloid-derived suppressor cells (mMDSCs), triggering USP51-mediated deubiquitination of estrogen receptor-α, thereby engaging membrane-bound O-acyltransferase domain-containing 1 signaling. This signaling cascade, in turn, promotes the infiltration of immunosuppressive mMDSCs and confers ferroptosis resistance to them in the tumor microenvironment. Targeting mMDSCs through GALR3 inhibition and ferroptosis induction impairs tumor progression and activates antitumor immunity in GBM mouse models. Remarkably, combining this approach with anti-PD1 therapy achieves durable and complete tumor regression in approximately 60% of tumor-bearing mice. Our study elucidates the molecular mechanism underlying GBM immunosuppression and highlights a promising therapeutic strategy to enhance GBM response to immunotherapy. Chen and colleagues report that the neuropeptide galanin impairs antitumor immunity in glioblastoma by interacting with its receptor GALR3 on monocytic myeloid-derived suppressor cells, promoting their infiltration and ferroptosis resistance.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1387-1405"},"PeriodicalIF":28.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01221-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Low-protein diet enhances antitumor immunity in pancreatic cancer through microbiota-derived UDP-galactose","authors":"Yueying Chen, Fulin Nian, Shengdi Wu, Tianli Yuan, Yifan Ma, Junyang Cao, Yuxiao Zhang, Wenfeng Liu, Wenqing Tang, Danying Zhang, Zi Li, Wei Lu, Fengwanni Wang, Xiulong Xia, Zhanju Liu, Si Zhang, Xizhong Shen, Xiaoming Hu, Ling Dong","doi":"10.1038/s43018-026-01241-z","DOIUrl":"10.1038/s43018-026-01241-z","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 10","pages":"1-1"},"PeriodicalIF":28.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01241-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coming full circle","authors":"Paul S. Mischel","doi":"10.1038/s43018-026-01219-x","DOIUrl":"10.1038/s43018-026-01219-x","url":null,"abstract":"Paul Mischel obtained his MD from Cornell University Medical College, trained in anatomic and neuropathology at UCLA and did post-doctoral research training in Louis Reichardt’s lab at HHMI/UCSF. He is the Fortinet Founders Professor, vice chair for research for the department of pathology, and deputy director of translational science and an institute scholar at Sarafan ChEM-H, Stanford University. Mischel leads Team eDyNAmiC of the Cancer Grand Challenges Program. He is a member of the National Academy of Medicine, a fellow of the AACR Academy, and past president of the American Society for Clinical Investigation.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 10","pages":"1471-1471"},"PeriodicalIF":28.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795718","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":"Rewiring immunity with in vivo CAR T cell engineering","authors":"Clare Y. Slaney, Rachel Xu, Shiyi Wu, Kevin Sek, Colin W. Pouton, Michael Dickinson, Michael H. Kershaw, Phillip K. Darcy","doi":"10.1038/s43018-026-01216-0","DOIUrl":"10.1038/s43018-026-01216-0","url":null,"abstract":"Ex vivo engineered chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of certain hematologic malignancies, yet manufacturing complexities and limited patient accessibility constrain its impact. In vivo CAR T cell engineering seeks to overcome these limitations by generating CAR T cells directly within an individual. This Perspective examines the rapidly evolving field of in vivo CAR T cell generation in oncology, outlines principles of lymphocyte targeting, discusses pharmacology and biodistribution and assesses emerging safety issues. We conclude with a translational outlook, highlighting both the opportunities and the outstanding questions that will define the path to clinical implementation. Darcy and colleagues discuss the recent technological advances in CAR T cell in vivo engineering and the challenges in its translational application for cancer therapy.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1330-1339"},"PeriodicalIF":28.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795738","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":"A lactate–α-ketoglutarate metabolic circuit in tumor-infiltrating regulatory T cells accelerates tumor progression by inducing NK cell senescence","authors":"Tiezhu Shi, Yufeng Ding, Ying Chen, Xiangyin Tan, Fangfang Qu, Dongwei Xu, Xinyu Liu, Yixue Li, Yan-fang Liu, Xiaolin Zhang, Guanzhen Yu, Jialiang Shao, Xiongjun Wang","doi":"10.1038/s43018-026-01210-6","DOIUrl":"10.1038/s43018-026-01210-6","url":null,"abstract":"Regulatory T (Treg) cells prevent autoimmune diseases but limit antitumor immunity. Tumor‑infiltrating Treg (Ti‑Treg) cells exhibit metabolic traits as potential antitumor targets. Here, we find that Ti-Treg cells upregulate glutamate dehydrogenase 1 (GDH1), increasing α-ketoglutarate (α-KG) levels. Elevated GDH1 in Ti-Treg cells accelerates tumor progression. Mechanistically, in a lactate rich microenvironment, GDH1 lactylation boosts α-KG production to fuel ALKBH5-mediated Wnt2 expression in Ti-Treg cells. Enhanced WNT2 promotes natural killer (NK) cell senescence. GDH1 inhibition or SLC16A1 deletion in Ti-Treg cells reduces NK senescence and improves adoptive NK transfer therapy. We reveal a lactate–α‑KG metabolic circuit driving NK senescence, offering therapeutic targets to boost antitumor immunity. Shi et al show that a lactate–α-ketoglutarate metabolic circuit in tumor-infiltrating regulatory T cells promotes WNT2-mediated senescence-like features in natural killer cells and disrupting this axis hinders tumor progression.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1368-1386"},"PeriodicalIF":28.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795690","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}