Nature cancer最新文献

{"title":"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/s43018-026-01222-2","DOIUrl":"10.1038/s43018-026-01222-2","url":null,"abstract":"Dietary interventions can influence cancer progression, yet the role of low-protein diets (LPDs) in pancreatic ductal adenocarcinoma (PDAC) immunotherapy is unclear. Here we show that an LPD suppresses PDAC progression in male mice by remodeling the gut microbiota and activating antitumor immunity. LPD promoted immune activation and drove an immunostimulatory tumor-associated macrophage phenotype. Microbiota depletion abolished these effects and fecal microbiota transplantation from LPD-fed donors transferred the protective phenotype to recipients. Mechanistically, LPD enriched Blautia coccoides, which produced uridine diphosphate (UDP)-galactose to activate the macrophage P2Y14R–STAT1 axis, inducing an immunostimulatory phenotype. Combining LPD, B. coccoides or UDP-galactose with anti-PD1 improved survival over anti-PD1 alone. In persons with advanced PDAC, reduced fecal B. coccoides and serum UDP-galactose correlated with poor outcomes. These findings establish that LPD reshapes the gut microbiota and metabolites to enhance antitumor immunity through the UDP-galactose–P2Y14R–STAT1 axis, offering a dietary strategy to improve PDAC immunotherapy. Chen et al. show that a low-protein diet increases the abundance of Blautia coccoides and its metabolite uridine diphosphate galactose, promoting antitumor immunity in pancreatic cancer.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 10","pages":"1572-1591"},"PeriodicalIF":28.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795727","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":"Local AI agent brings tumor board expertise to hematological malignancies","authors":"Sha Yu","doi":"10.1038/s43018-026-01228-w","DOIUrl":"10.1038/s43018-026-01228-w","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1161-1161"},"PeriodicalIF":28.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765244","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":"TIM3-targeted delivery of venetoclax overcomes drug resistance and reinvigorates NK cell activity in acute myeloid leukemia","authors":"Qiwei Wang \u0000 (, ), Jingyi Li \u0000 (, ), Xin Zeng \u0000 (, ), Lina Liu \u0000 (, ), Huan Lu \u0000 (, ), Yin Zhao \u0000 (, ), Yan Huang \u0000 (, ), Rui Wang \u0000 (, ), Chen Wang \u0000 (, ), Yingli Han \u0000 (, ), Yishan Ye \u0000 (, ), Yanmin Zhao \u0000 (, ), Jimin Shi \u0000 (, ), Yi Luo \u0000 (, ), Weiyan Zheng \u0000 (, ), Yongxian Hu \u0000 (, ), Shibing Wang \u0000 (, ), Xiangmin Tong \u0000 (, ), He Huang \u0000 (, ), Shanshan Pei \u0000 (, ), Pengxu Qian \u0000 (, )","doi":"10.1038/s43018-026-01217-z","DOIUrl":"10.1038/s43018-026-01217-z","url":null,"abstract":"Acute myeloid leukemia (AML) remains challenging, especially for older or unfit individuals who develop resistance to venetoclax (VEN)-based regimens. Although TIM3 represents a promising AML target, clinical blockade has yielded suboptimal outcomes. Here, we develop VINCENT (VEN-integrated natural killer cell engager targeting TIM3), a therapeutic platform combining anti-CD16 and anti-TIM3 antibodies with nanoformulated VEN. In VEN-resistant AML cell lines and patient-derived xenograft models, VINCENT overcomes resistance by enhancing VEN delivery, eliminating TIM3+ blasts and dysfunctional T cells and activating natural killer (NK) cells. In primary AML samples, VINCENT selectively kills drug-resistant blasts, with efficacy correlating with the NK cell-to-TIM3+ blast ratio. Single-cell transcriptomics reveals VINCENT depletes high-TIM3 blasts and remodels the immunosuppressive microenvironment toward immune competence. Collectively, VINCENT simultaneously addresses VEN resistance, NK cell dysfunction and immune evasion, offering a personalized option for elderly or unfit individuals with AML failing standard VEN regimens. Qian and colleagues report the characterization of venetoclax-loaded nanoparticles conjugated with anti-CD16 and anti-TIM3 antibodies, showing that the platform overcomes venetoclax resistance and reinvigorates natural killer cell activity in acute myeloid leukemia.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 10","pages":"1555-1571"},"PeriodicalIF":28.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723634","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":"Integrating AI in clinical decision-making","authors":"Vincenzo Giacco","doi":"10.1038/s43018-026-01230-2","DOIUrl":"10.1038/s43018-026-01230-2","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1162-1162"},"PeriodicalIF":28.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726701","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":"Charting intratumor heterogeneity from bench to bedside","authors":"Jonathan C. M. Wan, Nicholas McGranahan, Charles Swanton","doi":"10.1038/s43018-026-01198-z","DOIUrl":"10.1038/s43018-026-01198-z","url":null,"abstract":"Intratumor heterogeneity poses a fundamental challenge across the cancer care continuum, from diagnosis to treatment resistance and metastasis. Over recent decades, multiregion and multiomic profiling of tissue, together with functional studies and longitudinal plasma sampling, have revealed the dynamic and multidimensional evolution of tumor ecosystems. This complexity spans genetic and non-genetic mechanisms within cancer cells and their microenvironment. In this Review, we synthesize the current understanding of heterogeneity and evolution and discuss how these insights can inform the development of evolution-aware diagnostic and therapeutic strategies. Swanton and colleagues provide an overview on intratumor heterogeneity and cancer evolution arising from genetic factors and non-genetic regulation of cancer cells, the tumor microenvironment and the immune system.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1176-1188"},"PeriodicalIF":28.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689460","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":"Tumoral extracellular vesicles and particles reprogram interstitial macrophages in the lung to promote vascular permeability and metastasis","authors":"Shani Dror, Inbal Wortzel, Serena Lucotti, Yura Seo, Jianlong Li, Lee Shaashua, Irina Matei, Nancy Boudreau, Haiying Zhang, Maider Astorkia-Amiama, Doron Betel, Han Sang Kim, Jai Prakash, Jacqueline Bromberg, David Lyden","doi":"10.1038/s43018-026-01209-z","DOIUrl":"10.1038/s43018-026-01209-z","url":null,"abstract":"The mechanisms by which tumor-derived extracellular vesicles and particles (EVPs) promote vascular permeability during premetastatic niche formation remain unclear. Here, we show that tumor EVPs rapidly induce vascular leakiness within 1 h of administration in female mice, creating a permissive environment that enhances metastatic seeding. Rather than acting directly on endothelial cells, EVPs activate NF-κB and JAK–STAT signaling in interstitial macrophages, leading to IL-6 secretion and increased vascular permeability. Interstitial macrophage depletion markedly reduces EVP-induced vascular leakiness and metastasis. We identify extracellular vesicle-associated integrin α5 (ITGα5) as a major functional determinant of this process, promoting macrophage activation and IL-6 secretion without affecting EVP uptake. EVPs derived from colorectal cancer tumors with high ITGα5 similarly induce macrophage IL-6 secretion and vascular permeability. Together, these findings define an EVP–macrophage–IL-6 axis that drives vascular permeability during premetastatic niche formation and identify EVP-associated ITGα5 as a key mediator of metastatic progression and a potential therapeutic target. Dror et al. show that tumor-derived extracellular vesicles and particles reprogram interstitial macrophages during the formation of the lung premetastatic niche, thereby increasing vascular permeability and promoting metastatic potential.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1280-1299"},"PeriodicalIF":28.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01209-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679576","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":"Insights from the ESMO Targeted Anticancer Therapies Asia Congress 2026","authors":"Vincenzo Giacco","doi":"10.1038/s43018-026-01215-1","DOIUrl":"10.1038/s43018-026-01215-1","url":null,"abstract":"The latest ESMO Targeted Anticancer Therapies Asia Congress brought together researchers, clinicians and industry experts to discuss how advances in molecular oncology, cell therapies, artificial intelligence and translational science are shaping the next generation of cancer treatments. Opening the meeting, European Society For Medical Oncology (ESMO) president Fabrice André highlighted the society’s increasing global reach, with members spanning Europe, Asia and other regions worldwide. He emphasized the ESMO’s mission to support oncology professionals through education, consensus frameworks and clinical guidance while outlining the 2030 strategic priorities, including innovation in cancer treatment, real-world impact, prevention, survivorship and professional development.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1174-1175"},"PeriodicalIF":28.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679617","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":"Fc-optimized GITR antibody enhances a CD4 T cell–dendritic cell crosstalk to promote antitumor immunity","authors":"Yahel Avraham, Natasha Barth, Tzlil Yair Bar-On, Barak Toval, Aviya Habshush Menachem, Jasmine Blanga, Ella Herzog, Hagar Rotem, Yuval Shapir Itai, Tali Feferman, Moshe Biton, Rony Dahan","doi":"10.1038/s43018-026-01207-1","DOIUrl":"10.1038/s43018-026-01207-1","url":null,"abstract":"Targeting the stimulatory immune checkpoint glucocorticoid-induced TNFR-related protein (GITR) using agonistic monoclonal antibodies (mAbs) is a promising strategy for cancer immunotherapy that activates effector T cells and eliminates regulatory T cells. The antitumor activity of anti-GITR mAbs depends on the engagement of the fragment crystallizable (Fc) domain to their receptors (FcγRs); however, this has not been comprehensively investigated in human anti-GITR mAbs. Here, we used Fc protein and glycan engineering to modify the FcγR interactions of anti-GITR human mAbs and characterized them in humanized mice. We identified an Fc-optimized human IgG scaffold that enhances antitumor efficacy through multiple FcγR-mediated mechanisms, including regulatory T cell depletion and mutual engagement and activation of CD4+ T cells and dendritic cells, leading to antitumor cytotoxicity of CD4+ T cells and enhanced CD8+ T cell activity. Our findings suggest a strategy to optimize human anti-GITR mAbs, harnessing beneficial immune pathways to improve their therapeutic potential. Avraham et al. engineered an anti-GITR human antibody with an optimized Fc domain that engages the activating Fcγ receptors IIa and IIIa to enhance antitumor efficacy through the depletion of regulatory T cells and activation of CD4+ T cells and dendritic cells.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1419-1435"},"PeriodicalIF":28.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01207-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679530","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: IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial","authors":"Lukas Bunse, Katharina Lindner, Antje Wick, Angelika Freitag, Lisa-Marie Lanz, Dominic Edelmann, Abigail Suwala, Michael O. Breckwoldt, Inga Harting, Felix Sahm, Richard F. Schlenk, Anita Schmitt, Oliver Schnell, Jörg Hense, Martin Misch, Dietmar Krex, Monika Denk, Juliane Walz, Joachim P. Steinbach, Andreas von Deimling, Michael Schmitt, Theresa Bunse, Ghazaleh Tabatabai, Martin Bendszus, Isabel Poschke, Wolfgang Wick, Michael Platten","doi":"10.1038/s43018-026-01227-x","DOIUrl":"10.1038/s43018-026-01227-x","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1322-1322"},"PeriodicalIF":28.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01227-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670160","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":"Copper dependency in leukemia metabolism","authors":"Sarada Achyutuni, Jian Xu","doi":"10.1038/s43018-026-01205-3","DOIUrl":"10.1038/s43018-026-01205-3","url":null,"abstract":"Despite their crucial roles in physiology, the contributions of trace metals to cancer fitness and therapy response remain unclear. Combining a CRISPR screen with functional and metabolic studies, recent work identifies copper homeostasis as a key regulator of mitochondrial metabolism and liability in cerebrospinal fluid-infiltrating acute lymphoblastic leukemia cells.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1-3"},"PeriodicalIF":28.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670133","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}