Nature cancer最新文献

{"title":"Mesenchymal tumor features predict response to immune-checkpoint blockade in glioblastoma","authors":"","doi":"10.1038/s43018-026-01178-3","DOIUrl":"10.1038/s43018-026-01178-3","url":null,"abstract":"Multi-omics profiling of over 180 glioblastomas treated with immune-checkpoint blockade (ICB) revealed that the mesenchymal (MES) bulk transcriptional subtype and increased abundance of malignant cells exhibiting a MES-like transcriptional state are both predictive of improved survival after ICB. Transition away from the MES subtype was associated with poor ICB outcomes, suggestive of a mechanism of acquired resistance. These findings establish a framework for precision immunotherapy trial design in glioblastoma.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"880-881"},"PeriodicalIF":28.0,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258832","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 proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets","authors":"Shih-Chun A. Chu, Yi Hsiao \u0000 (, ), Chenwei Wang \u0000 (, ), Jennifer E. Kyle, Raghav Jain, Yamei Deng, Marina A. Gritsenko, Leanne E. Henry, Jonathan T. Lei, Yongchao Dou, Bahar Tercan, Zhiao Shi, Mahnoor N. Gondal, Chia-Feng Tsai \u0000 (, ), John M. Elizarraras, Rosalie K. Chu, Fengchao Yu, Sunil K. Joshi, Xiaojun Jing, Daniel A. Polasky, Karl K. Weitz, Ginny Xiaohe Li, Vanessa L. Paurus, Chaevien S. Clendinen, Athena A. Schepmoes, Priscila M. Lalli, Josie G. Eder, Javier E. Flores, Kelly G. Stratton, James C. Pino, Camilo Posso, Vladislav A. Petyuk, Tyler J. Sagendorf, Yuanwei Xu \u0000 (, ), Omar M. Ibrahim, Ronald J. Moore, Rui Zhao, Jin Chen, Matthew E. Monroe, Mathangi Thiagarajan, Galen Hostetter, Chelsea Newton, Eunkyung An, Ana I. Robles, Xu Zhang, Nathan J. Edwards, Yin Lu, Hui Zhang, Haitham Abdelhakim, Paul D. Piehowski, Mehdi Mesri, Richard D. Smith, Chandan Kumar-Sinha, Cristina E. Tognon, Jennifer Dunlap, Elie Traer, Li Ding, Jeffrey W. Tyner, Arul M. Chinnaiyan, Gilbert S. Omenn, Karin D. Rodland, Saravana M. Dhanasekaran, Sara J. C. Gosline, Alexey I. Nesvizhiskii, Bing Zhang, Tao Liu, Marcin P. Cieslik, Clinical Proteomic Tumor Analysis Consortium","doi":"10.1038/s43018-026-01175-6","DOIUrl":"10.1038/s43018-026-01175-6","url":null,"abstract":"Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematological malignancy. Here, to better define this clinically taxing and translationally challenging malignancy, we applied a multiomics approach, consisting of 13 modalities to analyze 173 treatment-naive individuals with AML. By integrating these ‘omes’, we identified distinct AML subtypes, genotype–phenotype associations, biomarkers and pathobiological mechanisms. Across the spectrum of primitive and committed AML, we found extensive metabolomic and lipidomic reprogramming driven by divergent MYC and mTOR activity. We linked metabolic changes to striking hyperacetylation of mitochondrial proteins in CEBPA-mutant AML. Protein-centric subtyping revealed a distinct NPM1-mutant subset characterized by outlier expression of FOXC1 and HOXB8/9. To nominate therapeutic targets across subtypes, we developed a multiomic machine-learning approach and validated MTA1 as a contributor to panobinostat resistance. Altogether our findings underscore the complex nature of AML and provide a clinically and translationally informed unified view that reveals coalescent phenotypes across multiomic layers. Chu et al. conducted multiomic analyses of samples from 173 treatment-naive individuals with acute myeloid leukemia, integrating proteogenomic and metabolomic modalities to identify subtypes, and developed a machine-learning approach to find therapy targets.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"993-1015"},"PeriodicalIF":28.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01175-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239658","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":"Publisher Correction: Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma","authors":"Jack Y. Ghannam, Julian Bryan, Jakob Weiss, Daniel Kovarsky, David Merrell, Conor Messer, Kristy Schlueter-Kuck, Geoffrey G. Fell, Mary Jane Lim-Fat, Gilbert Youssef, Rifaquat Rahman, Lei Qin, Geoffrey S. Young, J. Thomas Janes III, McKayla Van Orden, Kathleen L. Pfaff, Andrew Gans, Emma S. Lin, Raymond Y. Huang, Brian P. Danysh, Laxmi Parida, Shuqiang Li, Patrick Y. Wen, E. Antonio Chiocca, Donna Neuberg, Keith L. Ligon, Itay Tirosh, David A. Reardon, Gad Getz, Catherine J. Wu","doi":"10.1038/s43018-026-01197-0","DOIUrl":"10.1038/s43018-026-01197-0","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"1016-1016"},"PeriodicalIF":28.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01197-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239741","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":"Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy","authors":"Delin Kong, Tingting Yang, Mengyu Zhao, Lin Yang, Ruirui Jing, Youqin Feng, Shaohui Shi, Zhouning Lin, Shi Han, Cong Wei, Rongrong Chen, Qiqi Zhang, Jiazhen Cui, Tianning Gu, Xiujian Wang, Xia Li, Ye Meng, Xiaolin Yuan, Mingming Zhang, Linghui Zhou, Houli Zhao, Ruimin Hong, Simao Huang, Mi Shao, Xiaohui Si, Yingli Han, Shufen Wang, Xiangjun Zeng, Dawei Huo, Meng Zhang, Kejia Hu, Zenan Cen, Haiqiong Zheng, Guoqing Wei, Dongrui Wang, Yongxian Hu, Pengxu Qian, He Huang","doi":"10.1038/s43018-026-01187-2","DOIUrl":"10.1038/s43018-026-01187-2","url":null,"abstract":"Long-term persistence of chimeric antigen receptor (CAR)-T cells is essential for durable therapeutic efficacy but the mechanisms underlying CAR-T cell dysfunction remain unclear. On the basis of integrated analyses of clinical samples from participants with multiple myeloma and acute lymphoblastic leukemia treated with CAR-T cells, we show that rapid expansion of CAR-T cells after infusion is followed by a ‘diminution’ phase characterized by ferroptosis-associated features and elevated serum iron levels. In preclinical cancer models in female mice and ex vivo culture systems, excess intracellular iron impaired CAR-T cell function. Mechanistically, iron promoted ferroptosis by increasing mitochondrial reactive oxygen species and lipid peroxidation, in part through acyl-CoA synthetase long-chain family member 4 (ACSL4)-associated lipid remodeling. Targeting ferroptosis, particularly through genetic ablation of ACSL4 in CAR-T cells, substantially enhanced antitumor efficacy. Together, these findings identify iron-driven ferroptosis as a determinant of CAR-T cell dysfunction and a targetable barrier to durable CAR-T efficacy. Huang and colleagues report that elevated iron levels are associated with ferroptosis of chimeric antigen receptor (CAR)-T cells and inhibition of ferroptosis improves antitumor efficacy of CAR-T cells.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 8","pages":"1243-1260"},"PeriodicalIF":28.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218456","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":"Combination of paricalcitol with chemotherapy shows promise in phase 1 study of metastatic pancreatic cancer","authors":"","doi":"10.1038/s43018-026-01164-9","DOIUrl":"10.1038/s43018-026-01164-9","url":null,"abstract":"We conducted a prospective, phase 1 trial evaluating the safety and tolerability of the vitamin D receptor agonist paricalcitol given with first-line gemcitabine and albumin-bound paclitaxel in patients with metastatic pancreatic cancer. Paricalcitol was safely administered with chemotherapy, and on-treatment biopsies indicated favorable modulation of the tumor microenvironment.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"882-883"},"PeriodicalIF":28.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218480","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":"Hetairos is a histology-based artificial intelligence model for predicting central nervous system tumor methylation subtypes","authors":"Darui Jin \u0000 (, ), Artem Shmatko, Areeba Patel, Samuel Rutz, Lukas Friedrich, Rouzbeh Banan, Ramin Rahmanzade, Philipp Sievers, Stefan Hamelmann, Daniel Schrimpf, Kirsten Göbel, Henri Bogumil, Sybren L. N. Maas, Martin Sill, Felix E. Hinz, Abigail K. Suwala, Felix Keller, Antje Habel, Gleb Rukhovich, Ferdinand Zettl, Obada T. Alhalabi, Sebastian Ille, Jannik Sehring, Daniel Amsel, Benedikt Wiestler, Pedro Piovesan Lago, Bogdana Suchorska, Olfat Ahmad, Dominik Sturm, David Reuss, Pieter Wesseling, Adelheid Wöhrer, Frank L. Heppner, Ingmar Blümcke, Claire Delbridge, Martin Jakobs, Christel Herold-Mende, Sandro M. Krieg, Wolfgang Wick, David T. W. Jones, Stefan M. Pfister, Maysa Al-Hussaini, Yanghao Hou, Felipe D’Almeida Costa, Leonille Schweizer, Luca Bertero, Till Acker, Arnault Tauziede-Espariat, Pascale Varlet, Doron Merkler, Kristof Egervari, Hildegard Dohmen, Pablo Zoroquiain, Roger Gejman, Sebastian Brandner, Xiangzhi Bai, Andreas von Deimling, Felix Sahm, Moritz Gerstung","doi":"10.1038/s43018-026-01186-3","DOIUrl":"10.1038/s43018-026-01186-3","url":null,"abstract":"Molecular testing is essential for classifying central nervous system (CNS) tumors, with methylation profiling providing the highest diagnostic granularity. However, this requires more resources and time than conventional hematoxylin and eosin (H&E) histopathology, which is widely available globally. Here we propose Hetairos, an artificial intelligence algorithm that predicts 102 methylation-based CNS tumor subtypes from digital H&E slides. Built and validated on 9,606 patients and over 11,000 slides from 11 centers across four continents, Hetairos identified 50–70% of cases with high confidence, achieving an accuracy of 0.87 for its highest-rated predictions. Hetairos outperformed five board-certified neuropathologists in a direct histology-only comparison (0.68 versus 0.30). Prospective evaluation in routine diagnostics confirmed its performance, reducing turnaround time from 12 days (molecular testing) to 12 min. Hetairos supports diagnostic decision-making across the full spectrum of pediatric and adult CNS tumors by narrowing differential diagnoses and guiding efficient testing. Jin et al. developed an artificial intelligence tool that leverages histology to predict methylation-based central nervous system tumor subtypes and validated it for tumor classification, demonstrating high confidence and accuracy across clinical cohorts.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"884-898"},"PeriodicalIF":28.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01186-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218466","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":"First-line durvalumab in combination with trastuzumab deruxtecan in women with locally advanced unresectable or metastatic, hormone-receptor-negative, HER2-low breast cancer: multicenter, open-label, phase 1b/2 BEGONIA platform trial","authors":"Peter Schmid, Seock-Ah Im, Zbigniew Nowecki, Piotr J. Wysocki, Jacek Jassem, Kyung Hae Jung, Simon Lord, Jon Armstrong, Ross Stewart, Petra Vuković, Neelima Denduluri, Yeon Hee Park","doi":"10.1038/s43018-026-01181-8","DOIUrl":"10.1038/s43018-026-01181-8","url":null,"abstract":"More effective therapies are required for advanced breast cancer. We report results from 58 women with locally advanced unresectable or metastatic hormone-receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-low breast cancer enrolled in arm 6 of the multicenter, open-label phase 1b/2 BEGONIA platform trial, who received durvalumab (1,120 mg) plus trastuzumab deruxtecan (T-DXd; 5.4 mg kg−1) intravenously every 3 weeks as first-line treatment. Objective response rate (ORR) and safety were primary endpoints; duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Median follow-up was 20.6 months (range: 1–37). ORR was 62.1% (95% confidence interval (CI): 48.4–74.5), which did not meet the protocol-specified objective of 38/57 (66.6%) responses. Median DoR was 15.2 months (95% CI: 8.44–not calculable), PFS was 12.6 months (95% CI: 8.4–16.3) and OS was 30.3 months (95% CI: 18.8–not calculable). The safety profile of the combination treatment was consistent with those of the individual therapies. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 20.7% of participants (grades 1 and 2, 19.0%; grade 5, 1.7%). Durvalumab plus T-DXd demonstrated clinically relevant efficacy for first-line treatment of metastatic HR-negative, HER2-low breast cancer, with no unexpected toxicities observed. ClinicalTrials.gov identifier: NCT03742102 . In this phase 1/2 BEGONIA platform trial, Schmid and colleagues evaluated the safety and efficacy of durvalumab and trastuzumab deruxtecan in participants with locally advanced unresectable or metastatic hormone-receptor-negative breast cancer with low human epidermal growth factor receptor 2.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"983-992"},"PeriodicalIF":28.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01181-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205011","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":"Bacterial engineering for cancer therapy","authors":"Noah Chen, Zaofeng Yang, Nicholas Arpaia","doi":"10.1038/s43018-026-01171-w","DOIUrl":"10.1038/s43018-026-01171-w","url":null,"abstract":"One of the most critical challenges in cancer therapy is the effective and specific targeting of tumors. The specific accumulation of bacteria within tumor tissue has been exploited for the delivery of therapeutic payloads, including cytotoxic agents and cancer immunotherapeutics, to the tumor site; however, such bacteria-based cancer therapies face challenges related to insufficient colonization and limited efficacy in the clinic. In this Perspective, we discuss mechanisms of bacterial tumor colonization and methods to enhance them, the antitumor mechanisms of bacteria, and considerations for payload selection and delivery. In this Perspective, Arpaia and colleagues provide an overview of bacteria-based cancer therapies, discussing the potential of engineered bacteria as living drug delivery systems as well as the challenges to their implementation in the clinic.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 9","pages":"1340-1349"},"PeriodicalIF":28.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163586","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":"Intrathecal nivolumab in metastatic solid tumors with leptomeningeal disease: dose escalation part of the multicenter IT-PD1/NOA-26 phase 1 trial","authors":"Ghazaleh Tabatabai, Isabel Ramirez, Beatrix Welte, Paula Bombach, Hannes Becker, Denise Bernhardt, Regine Mayer-Steinacker, Friedegund Meier, Nicolas Neidert, Roland Roelz, Iris Mildenberger, Lukas Bunse, Michael Platten, Ulrich Herrlinger, Uwe M. Martens, Ulrike Ernemann, Manuela Neumann, Marcos Tatagiba, Lina Maria Serna-Higuita, Peter Martus, Mirjam Renovanz","doi":"10.1038/s43018-026-01185-4","DOIUrl":"10.1038/s43018-026-01185-4","url":null,"abstract":"Leptomeningeal metastatic disease (LMD) of solid tumors represents a cancer stage with high unmet therapeutic need. Here we report results from the dose escalation part of a multicenter phase 1 trial investigating intraventricular nivolumab, now continuing in the expansion part. Eligible participants had LMD from tumors with an approval for intraveneous PD1/PDL1 therapy or high tumor mutational burden. The primary endpoint was safety across four dose levels (20, 30, 40 and 50 mg) with each cohort reviewed by an independent data safety monitoring board before escalation. The secondary endpoint was overall survival. Exploratory endpoints included participant-reported outcome measures. Of 30 enrolled participants, 24 received at least one dose (intention-to-treat population) and 18 completed predefined safety evaluations (per-protocol population). One dose-limiting toxicity occurred at 40 mg. The primary endpoint was met and the recommended fixed dose for the ongoing expansion part is 50 mg. Median overall survival (OS) was 6.6 months. The 6-month, 12-month and 18-month OS rates were 55.0% (95% confidence interval (CI): 37.5–80.6%), 33.3% (95% CI: 17.8–62.4%) and 16.7% (95% CI 6.03–46.1%), respectively. Participant-reported quality of life remained stable. Intraventricular nivolumab has demonstrated safety and feasibility (ClinicalTrials.gov: NCT05112549 ). Tabatabai et al. evaluated the safety of intrathecal administration of nivolumab in participants with leptomeningeal disease in the IT-PD1/NOA-26 phase 1 clinical trial.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 7","pages":"1094-1103"},"PeriodicalIF":28.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-026-01185-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163544","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":"Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma","authors":"Jack Y. Ghannam, Julian Bryan, Jakob Weiss, Daniel Kovarsky, David Merrell, Conor Messer, Kristy Schlueter-Kuck, Geoffrey G. Fell, Mary Jane Lim-Fat, Gilbert Youssef, Rifaquat Rahman, Lei Qin, Geoffrey S. Young, J. Thomas Janes III, McKayla Van Orden, Kathleen L. Pfaff, Andrew Gans, Emma S. Lin, Raymond Y. Huang, Brian P. Danysh, Laxmi Parida, Shuqiang Li, Patrick Y. Wen, E. Antonio Chiocca, Donna Neuberg, Keith L. Ligon, Itay Tirosh, David A. Reardon, Gad Getz, Catherine J. Wu","doi":"10.1038/s43018-026-01179-2","DOIUrl":"10.1038/s43018-026-01179-2","url":null,"abstract":"The determinants of immune checkpoint blockade (ICB) response in glioblastoma (GBM) with wild-type isocitrate dehydrogenase remain poorly understood. Here we profiled 181 ICB-treated GBM cases using bulk DNA sequencing, bulk RNA sequencing and single-nucleus RNA sequencing to investigate the genomic features associated with ICB outcomes. Baseline tumor transcriptional subtype was predictive of overall survival following ICB, with mesenchymal (MES) GBM associated with improved outcomes to ICB but not standard chemoradiation. Non-MES-associated genetic lesions, including those in PDGFRA and CDKN2A, were associated with worse survival following ICB but not standard therapy. Tumor mutational burden was not predictive of outcomes. Survival was associated with pre-ICB enrichment for MES-like malignant cells, marked by high human leukocyte antigen class I expression and greater T cell infiltration. Paired tumor analyses linked ICB exposure to outgrowth of subclones harboring lesions associated with non-MES subtypes, supporting MES-to-non-MES transition as a common trajectory of acquired resistance to ICB, distinct from standard chemoradiation. In a large cohort of participants with immune-checkpoint-blockade-treated glioblastoma, Ghannam et al. show that baseline mesenchymal transcriptional state predicts therapy response and transition to nonmesenchymal state results in acquired resistance.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"7 6","pages":"964-982"},"PeriodicalIF":28.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157124","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}