Nature cancer最新文献

{"title":"TMEM87A suppresses ferroptosis and increases cancer immunotherapy resistance by maintaining the Golgi apparatus pH homeostasis.","authors":"Jing Li, Yuhan Zhou, Xiong Li, Songlin Yin, Yuan Gao, Haotian Shang, Yongfeng Lai, Liguo Yang, Ying Xue, Xiaoxiao Li, Yan Li, Zhenzhen Chang, Jing Chen, Xiang Cheng, Xiaoyan Zhang, Qian Chu, Fujia Lu, Weimin Wang","doi":"10.1038/s43018-026-01156-9","DOIUrl":"10.1038/s43018-026-01156-9","url":null,"abstract":"<p><p>Most membrane-bound organelles have been linked to the initiation and execution of ferroptosis. However, the role of the Golgi apparatus and its resident proteins in ferroptosis remain elusive. Here we show that ferroptosis inducer triggers rapid oxidation of Golgi membrane lipids in the early phase of ferroptosis, resulting in disruption of Golgi pH. The Golgi-localized transmembrane protein TMEM87A is identified to mediate ferroptosis resistance through buffering Golgi pH. Depletion of TMEM87A leads to Golgi overacidification, which impairs FSP1-mediated reduction of coenzyme Q. In vivo, TMEM87A ablation suppresses the progression of multiple murine tumors including melanoma, colorectal cancer and liver cancer. TMEM87A ablation also enhances antitumor T cell responses and potentiates PD1 blockade therapy. Clinically, tumoral TMEM87A expression negatively correlates with immunotherapy response and treatment outcome. Our study reveals that TMEM87A functions as a suppressor of tumoral ferroptosis by maintaining Golgi pH homeostasis and targeting TMEM87A is potent to augment cancer immunotherapy.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776378","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":"Heterogeneity and plasticity of cancer-associated fibroblasts","authors":"Sneha Pramod,&nbsp;Hagar Lavon,&nbsp;Ruth Scherz-Shouval,&nbsp;Mara H. Sherman","doi":"10.1038/s43018-026-01146-x","DOIUrl":"10.1038/s43018-026-01146-x","url":null,"abstract":"Fibroblasts sense and respond to contextual cues to support tissue structure and function. In cancer, they engage a dysregulated wound-healing response that profoundly shapes tumor composition and progression. Efforts to therapeutically target these cancer-associated fibroblasts (CAFs) have been complicated by their heterogeneity and plasticity. However, recent advances, particularly in single-cell and spatial technologies, have greatly improved the understanding of the phenotypic consequences of distinct CAF states and functions. Here we review the current understanding of CAFs as heterogeneous, instructive regulators of tumor microenvironments across anatomic sites and highlight key challenges for the future. Sherman and colleagues provide an overview of the current understanding of the heterogeneity and plasticity of cancer-associated fibroblasts.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 4","pages":"583-596"},"PeriodicalIF":28.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729465","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":"Advances in predicting T cell epitope recognition for cancer immunotherapy.","authors":"David Gfeller, Julien Racle, Alexandre Harari, Giancarlo Croce","doi":"10.1038/s43018-026-01144-z","DOIUrl":"https://doi.org/10.1038/s43018-026-01144-z","url":null,"abstract":"<p><p>T cell recognition of malignant cells is central to cancer immunotherapy. This process is elicited by interactions between T cell receptors (TCRs) and antigenic peptides displayed on major histocompatibility complex molecules. Sequencing technologies enable characterization of genomic, transcriptomic and epigenetic alterations that can give rise to epitopes in cancer cells, alongside TCR repertoire profiling in T cells. An important challenge is to determine which peptides are recognized by T cells and which TCRs mediate this recognition. This Perspective highlights how technological and computational advances have improved epitope predictions, shed light on TCR-epitope recognition and could help leverage TCR repertoires for therapeutic innovations in cancer immunotherapy.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699197","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":"Predictive value of early PSMA upregulation for the response to enzalutamide ± 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer: substudy of the randomized, phase 2 ENZA-p trial","authors":"Louise Emmett,&nbsp;Mina Swiha,&nbsp;Nathan Papa,&nbsp;Shalini Subramaniam,&nbsp;Megan Crumbaker,&nbsp;Anthony M. Joshua,&nbsp;Andrew Nguyen,&nbsp;Andrew Weickhardt,&nbsp;Sze-Ting Lee,&nbsp;Siobhan Ng,&nbsp;Roslyn J. Francis,&nbsp;Jeffrey C. Goh,&nbsp;David A. Pattison,&nbsp;Sarennya Pathmanandavel,&nbsp;Thomas Hope,&nbsp;Narjess Ayati,&nbsp;Michael S. Hofman,&nbsp;Shahneen Sandhu,&nbsp;Claire Niu,&nbsp;Andrew J. Martin,&nbsp;Hayley Thomas,&nbsp;Martin R. Stockler,&nbsp;Ian D. Davis,&nbsp;on behalf of the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group","doi":"10.1038/s43018-026-01140-3","DOIUrl":"10.1038/s43018-026-01140-3","url":null,"abstract":"Prostate-specific membrane antigen (PSMA) receptor expression alters with androgen blockade in metastatic castrate-resistant prostate cancer (mCRPC). We evaluated the frequency and significance of early PSMA-positron emission tomography (PET) standardized uptake value (SUV) mean change with enzalutamide ± 177Lu-PSMA-617. ENZA-p is a randomized trial. Participants had mCRPC and 68Ga-PSMA positive disease. Participants were randomized (1:1) to enzalutamide or enzalutamide + 177Lu-PSMA-617, undergoing 68Ga-PSMA-PET–computed tomography (CT) at baseline and day 15 of enzalutamide treatment. 68Ga-PSMA-PET–CT were quantified for SUV mean. The study evaluated early SUV mean change, and prostate-specific-antigen (PSA) progression-free survival (PSA-PFS), 50% PSA-decline and overall survival. We randomized 162 participants, of whom 154 of 160 (96%) treated participants had PSMA-PET at day 15. SUV mean increased in 105 of 154 (68%) participants. Median PSA-PFS with increasing SUV mean was 5.8 (95% confidence interval (CI) 4.0–8.7) versus 13.1 (95%CI 10.5–17.0) months for enzalutamide versus enzalutamide + 177Lu-PSMA-617 (hazard ratio (HR) 0.38, 95%CI 0.25–0.58; log-rank P &lt; 0.001). With decreasing SUV mean, median PSA-PFS was 12.5 (95%CI 3.2–23.6) versus 13.3 (95%CI 9.6–22.2) months for enzalutamide versus enzalutamide + 177Lu-PSMA-617 (HR 0.80, 95%CI 0.42–1.53; log-rank P = 0.5). The interaction between SUV mean increase or decrease and treatment arm for PSA-PFS was P = 0.055. Early PSMA-SUV mean increase is frequent, predicting shorter PSA-PFS with first-line enzalutamide in mCRPC. The addition of 177Lu-PSMA-617 to enzalutamide mitigated the short PSA-PFS in those with early PSMA SUV mean increase. ClinicalTrials.gov registration: NCT04419402 . Emmett and colleagues evaluate the frequency, magnitude and clinical significance of early prostate-specific membrane antigen (PSMA) upregulation in patients with metastatic castrate-resistant prostate cancer treated with enzalutamide with or without 177Lu-PSMA-617.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 4","pages":"622-630"},"PeriodicalIF":28.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691153","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":"Multi-omic characterization of nasopharyngeal carcinoma delineates the subtype-specific landscape of response to induction chemotherapy.","authors":"Yingqin Li, Dongxue Wang, Chunxian Ou, Zaoqu Liu, Xianfeng Shao, Yuheng Zhao, Xinxin Zhang, Jiaxi Shen, Qingmei He, Xu Liu, Yuan Zhang, Xiaoyu Liang, Yaoyi Li, Huimin Huang, Linhai Xie, Gaoyuan Wang, Yelin Liang, Kaixuan Li, Meng Yan, Qianying Yang, Linglong Tang, Lei Chen, Yin Zhao, Sha Xu, Ying Sun, Jia-Xing Yue, Na Liu, Aihua Sun, Jun Ma, Fuchu He","doi":"10.1038/s43018-026-01149-8","DOIUrl":"https://doi.org/10.1038/s43018-026-01149-8","url":null,"abstract":"<p><p>Gemcitabine and cisplatin (GP) serve as first-line induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC), yet predictive markers are lacking. Here we performed multi-omics profiling, including proteomics, phosphoproteomics, genomics and transcriptomics, on 240 patients with NPC who were receiving GP-IC or concurrent chemoradiotherapy (CCRT) alone. Through multi-omic integration, we identified three proteomic subtypes with distinct therapeutic vulnerabilities. The S1 subtype showed a predominant interferon-γ response and had favorable outcomes with CCRT alone. The S2 subtype featured copy-number-driven cell cycle activation, deriving benefits from GP-IC. The immune-exhausted S3 subtype exhibited high IgA⁺ plasma cell infiltration and was resistant to GP-IC but responded to anti-PD-1 therapy. Single-cell RNA sequencing confirmed interaction between IgA⁺ plasma cells and CD8⁺ T cells in nonresponders. Validation from three phase III trials and spatial analyses demonstrated that high IgA⁺ plasma cell infiltration predicted GP-IC resistance but benefited from anti-PD-1 therapy. This study delineates a subtype-specific landscape of GP-IC response and may inform personalized treatment in NPC.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691135","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":"Harnessing foundation models for digital pathology without re-training","authors":"Zhiping Xiao,&nbsp;Sheng Wang","doi":"10.1038/s43018-025-01108-9","DOIUrl":"10.1038/s43018-025-01108-9","url":null,"abstract":"Applications of digital pathology in clinical oncology have largely depended on the requirement for labeled data and model re-training. A study now presents PRET, a training-free framework with robust performance for pan-cancer diagnosis that adapts pathology foundation models to diverse tasks at inference stage, from screening and subtyping tasks to segmentation and metastasis detection tasks.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 4","pages":"559-561"},"PeriodicalIF":28.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616402","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":"Single-cell and spatial profiling in cancer biology and clinical oncology","authors":"Chris J. Frangieh,&nbsp;Joy Linyue Fan,&nbsp;Johannes C. Melms,&nbsp;Parin Shah,&nbsp;Elham Azizi,&nbsp;Benjamin Izar","doi":"10.1038/s43018-026-01142-1","DOIUrl":"10.1038/s43018-026-01142-1","url":null,"abstract":"Multiple single-cell and spatial genomics tools have transformed our ability to deconvolve intricate diseases, including cancer. Analysis of complex, multimodal data has provided insights into genomics, cellular states and interactions in tumor ecosystems, enabling the dissection of salient biology and expanding our understanding of drug response, resistance and target discovery. However, several challenges remain before these methods can achieve their full clinical potential. Here, we discuss opportunities, barriers and potential solutions, including sample acquisition and preservation approaches, profiling methods and analytical tools for heterogeneous populations, and we provide recommendations for robust, reproducible use of these technologies in clinical settings. Izar and colleagues review the insights into cancer biology gained via single-cell analyses and spatial profiling and overview the challenges and opportunities associated with the implementation of these approaches to guide clinical discovery.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 4","pages":"597-607"},"PeriodicalIF":28.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616348","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 tumor-derived metabolite primes the leptomeningeal pre-metastatic niche.","authors":"Shi Li, Cyrus M Ghajar","doi":"10.1038/s43018-026-01138-x","DOIUrl":"https://doi.org/10.1038/s43018-026-01138-x","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616395","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":"PRET is a few-shot system for pan-cancer recognition without example training","authors":"Yi Li,&nbsp;Ziyu Ning,&nbsp;Tianqi Xiang,&nbsp;Qixiang Zhang,&nbsp;Zhihao Lin,&nbsp;Min Yi,&nbsp;Feiyan Feng,&nbsp;Baozhen Zeng,&nbsp;Xuexia Qian,&nbsp;Lu Sun,&nbsp;Jiace Qin,&nbsp;Ling Xiang,&nbsp;Chao Fan,&nbsp;Tian Qin,&nbsp;Qian Wang,&nbsp;Xiu-Wu Bian,&nbsp;Kun-Hsing Yu,&nbsp;Kang Zhang,&nbsp;Qingling Zhang,&nbsp;Xiaomeng Li","doi":"10.1038/s43018-026-01141-2","DOIUrl":"10.1038/s43018-026-01141-2","url":null,"abstract":"Pathological examination stands as the cornerstone in cancer diagnosis, impacting millions worldwide annually. With the shortage of pathologists globally, artificial intelligence (AI) has emerged rapidly to automate the diagnostics process. However, conventional AI models require substantial labeled data for each disease, posing huge challenges in scalability and practicality. Therefore, we introduce PRET (pan-cancer recognition without examples training), a few-shot system to achieve flexible, scalable, and effective cancer recognition across diverse organs, hospitals and tasks without training. Evaluated on 23 international benchmarks comprising 4,484 whole-slide images, our method outperforms existing approaches across 20 tasks, achieving over 97% area under the curve on 15 benchmarks with a maximum improvement of 36.76%. Notably, PRET delivers clinical-grade diagnostic performance in lymph node metastasis detection using only eight slide examples, outperforming 11 pathologists. By offering a flexible and cost-effective solution for pan-cancer recognition, PRET paves the way for accessible and equitable AI-based pathology systems, particularly benefiting minority populations and underserved regions. Li et al. present PRET, a few-shot system for pan-cancer detection not requiring model fine-tuning, validated it in multicenter datasets and found that it outperformed existing approaches across tasks and pathologists in lymph node metastasis detection.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 4","pages":"684-698"},"PeriodicalIF":28.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616377","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":"Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling.","authors":"Yang Huang, Yifan Hou, Jiahui Yang, Wanqi Yang, Hanxin Liu, Haibao Peng, Xiaohui Li, Jiaxu Zhao, Ye Zhang, Rui Zeng, Youming Zeng, Cheng Li, Qiangqiang Zhang, Yudan Chi","doi":"10.1038/s43018-026-01145-y","DOIUrl":"https://doi.org/10.1038/s43018-026-01145-y","url":null,"abstract":"<p><p>The choroid plexus acts as a crucial barrier in leptomeningeal metastasis (LM), yet the mechanisms through which cancer cells modulate supportive premetastasis niches remain unclear. Here, we show that remodeling of the metabolic microenvironment modifies the structure and function of choroid plexus vessels, which destroy vascular integrity to facilitate metastatic colonization. An abnormal increase in the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid and choroid plexus indicates a predisposition. Before initially invading the choroid plexus through cancer cells, 5-HIAA-containing extracellular vesicles specifically target vessels, resulting in vascular distortion, abnormal hemodynamics, compromised permeability and facilitation of cancer cell traversal. Mechanistically, aryl hydrocarbon receptor pathway activation by 5-HIAA is linked to choroid plexus vascular remodeling, characterized by aberrant expression of mechanoreceptors and tight junction proteins. Hence, our findings underscore the key role of 5-HIAA in supportive niche formation and highlight metabolic determinants that govern choroidal plasticity to effectively prevent metastatic colonization in LM initiation.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616426","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}