Cancer CellPub Date : 2026-09-14Epub Date: 2026-07-27DOI: 10.1016/j.ccell.2026.06.020
Georgia Lattanzi, Daniel Hollern
{"title":"Tumor-infiltrating plasma cell targets as a source for immunotherapies.","authors":"Georgia Lattanzi, Daniel Hollern","doi":"10.1016/j.ccell.2026.06.020","DOIUrl":"10.1016/j.ccell.2026.06.020","url":null,"abstract":"<p><p>Tumor-infiltrating plasma cells are key responders to immunotherapy. In this issue of Cancer Cell, Meyerhoff et al. show that plasma cells from lung lesions of anti-PD-1-treated patients target citrullinated proteins. Engineering CAR T cells with these plasma cells scFv reveals anti-tumor specificity without adverse effects, identifying therapeutic opportunities.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1733-1734"},"PeriodicalIF":56.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599345","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}
Cancer CellPub Date : 2026-09-14Epub Date: 2026-07-29DOI: 10.1016/j.ccell.2026.06.017
Ye Li, Huihui Fan, Guohui Wang, Xin Wang, Rafet Basar, Maliha Nuzhat Munir, Nadima Uprety, Rejeena Shrestha, Ludovica La Posta, Bin Liu, Jeffrey Wilson, Prashant Menon, Natalie Wall Fowlkes, Patrick Zhang, Enli Liu, Gary M Deyter, Luis Muniz-Feliciano, Pinaki P Banerjee, May Daher, David Marin, Eleonora Dondossola, Navin Varadarajan, Elizabeth J Shpall, Katayoun Rezvani
{"title":"Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction.","authors":"Ye Li, Huihui Fan, Guohui Wang, Xin Wang, Rafet Basar, Maliha Nuzhat Munir, Nadima Uprety, Rejeena Shrestha, Ludovica La Posta, Bin Liu, Jeffrey Wilson, Prashant Menon, Natalie Wall Fowlkes, Patrick Zhang, Enli Liu, Gary M Deyter, Luis Muniz-Feliciano, Pinaki P Banerjee, May Daher, David Marin, Eleonora Dondossola, Navin Varadarajan, Elizabeth J Shpall, Katayoun Rezvani","doi":"10.1016/j.ccell.2026.06.017","DOIUrl":"10.1016/j.ccell.2026.06.017","url":null,"abstract":"<p><p>Allogeneic CAR-engineered NK cells enable scalable off-the-shelf therapy, yet donor heterogeneity remains a major barrier to consistent potency. Building on our clinical experience with cord blood-derived CAR NK cells, we identified an immature CD16<sup>-</sup>CD161<sup>-</sup> double-negative (DN) NK subset associated with poor outcomes. Following CAR engineering, DN-derived NK cells remained hypofunctional yet exhibited exaggerated trogocytosis, accumulating high levels of cognate antigen and forming an intra-product trogocytic-antigen sink (TAS) that diverted CAR engagement from tumor targets and promoted on-target off-tumor interactions within the product. Consequently, CD16<sup>+</sup>CD161<sup>+</sup> double-positive (DP) effectors exposed to the TAS underwent sustained activation, metabolic stress, fratricide, reduced viability, programmed cell death, and progressive exhaustion, culminating in impaired persistence and tumor control. Pre-manufacturing DN depletion eliminated the TAS and restored DP antitumor activity across hematologic and solid tumor models. Together, these findings define a donor subset-driven mechanism of CAR NK dysfunction and provide a manufacturing strategy to improve antitumor potency.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1799-1814.e11"},"PeriodicalIF":56.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618500","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}
Cancer CellPub Date : 2026-09-14Epub Date: 2026-08-10DOI: 10.1016/j.ccell.2026.06.021
Haochen Yang, Chenqi Xu
{"title":"Latent tumor killers awakened.","authors":"Haochen Yang, Chenqi Xu","doi":"10.1016/j.ccell.2026.06.021","DOIUrl":"10.1016/j.ccell.2026.06.021","url":null,"abstract":"<p><p>In this issue of Cancer Cell, Kehl et al. construct a single-cell atlas of bone marrow T cells from patients with bone marrow-resident malignancies, identifying tumor-reactive populations existing in a state of latent competence. A 15-gene signature identifies this subset, which is expanded by immunotherapies and predicts clinical responses.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1727-1729"},"PeriodicalIF":56.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705490","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}
Cancer CellPub Date : 2026-09-14Epub Date: 2026-08-28DOI: 10.1016/j.ccell.2026.08.018
Boya Wang, George Wright, Julius C Enssle, Xin Yu, James D Phelan, Yandan Yang, Arthur Shaffer, Arvin E Ruiz, Da Wei Huang, Zana Coulibaly, Michael Kelly, Bao Tran, Stefania Pittaluga, Mark Roschewski, Wyndham H Wilson, Thomas Oellerich, Giorgio Inghirami, Louis M Staudt
{"title":"Axes of biological variation in diffuse large B cell lymphoma.","authors":"Boya Wang, George Wright, Julius C Enssle, Xin Yu, James D Phelan, Yandan Yang, Arthur Shaffer, Arvin E Ruiz, Da Wei Huang, Zana Coulibaly, Michael Kelly, Bao Tran, Stefania Pittaluga, Mark Roschewski, Wyndham H Wilson, Thomas Oellerich, Giorgio Inghirami, Louis M Staudt","doi":"10.1016/j.ccell.2026.08.018","DOIUrl":"10.1016/j.ccell.2026.08.018","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1895-1901"},"PeriodicalIF":56.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850028","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}
Cancer CellPub Date : 2026-09-14Epub Date: 2026-07-24DOI: 10.1016/j.ccell.2026.06.018
Hiroki Kobayashi, Tadashi Iida, Yosuke Ochiai, Akihiro Sakai, Ruth A White, Yi Zeng, Xiaofei Zhi, Jin Qian, Feijing Wu, Biyun Zheng, Junya Arai, Masahiro Hata, Hualong Zheng, Puran Zhang, Shuang Li, Quin T Waterbury, Jonathan S LaBella, Harry Nagendra, Leah B Zamechek, Atsushi Ogura, Mitsuro Kanda, Holger K Eltzschig, Susan L Woods, Daniel L Worthley, Atsushi Enomoto, Timothy C Wang
{"title":"A self-amplifying nerve-fibroblast circuit drives colorectal cancer progression.","authors":"Hiroki Kobayashi, Tadashi Iida, Yosuke Ochiai, Akihiro Sakai, Ruth A White, Yi Zeng, Xiaofei Zhi, Jin Qian, Feijing Wu, Biyun Zheng, Junya Arai, Masahiro Hata, Hualong Zheng, Puran Zhang, Shuang Li, Quin T Waterbury, Jonathan S LaBella, Harry Nagendra, Leah B Zamechek, Atsushi Ogura, Mitsuro Kanda, Holger K Eltzschig, Susan L Woods, Daniel L Worthley, Atsushi Enomoto, Timothy C Wang","doi":"10.1016/j.ccell.2026.06.018","DOIUrl":"10.1016/j.ccell.2026.06.018","url":null,"abstract":"<p><p>Nerves and cancer-associated fibroblasts (CAFs) have each been shown to regulate cancer progression directly. However, whether these cells interact to control tumor progression remains largely unknown. We show that in colorectal cancer (CRC), cholinergic stimulation induces CHRM3/Gq-dependent NTN1 secretion from CAFs, which in turn enhances intratumor cholinergic innervation. Within this feedforward loop, cholinergic stimulation promotes CRC growth directly through tumoral CHRM3/Gq-mediated YAP activation, while CAF-derived NTN1 promotes CRC growth and epithelial-to-mesenchymal transition-like programs via UNC5B-PI3K/AKT signaling. Chemogenetic activation of cholinergic neurons or fibroblast activation of the M3 receptor/Gq promotes tumoral YAP and AKT signaling and CRC progression. Conversely, blocking CHRM3 or NTN1 suppresses these pathways and improves mouse survival. In human CRC, high NTN1 expression is associated with a mesenchymal-like subtype and poor patient outcomes. These findings suggest that the neuro-mesenchymal interaction is central to CRC progression and could be therapeutically targeted with a CHRM3 antagonist or NTN1-blocking antibody.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"1862-1881.e18"},"PeriodicalIF":56.1,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583826","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":"Ensemble learning of pathology foundation models for precision oncology","authors":"Xiangde Luo,Xiyue Wang,Feyisope Eweje,Xiaoming Zhang,Juan Luis Gomez Marti,Sarah Cascarino,Sen Yang,Yuchen Li,Ryan Quinton,Jinxi Xiang,Yuanfeng Ji,Zhe Li,Yijiang Chen,Colin Bergstrom,Ted Kim,Francesca Maria Olguin,Kelley Yuan,Matthew Abikenari,Andrew Heider,Sierra Willens,Sanjeeth Rajaram,Robert West,Joel Neal,Adam Schoenfeld,Maximilian Diehn,Chad Vanderbilt,Ruijiang Li","doi":"10.1016/j.ccell.2026.08.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.08.008","url":null,"abstract":"Histopathology is essential for cancer diagnosis and treatment selection, and pathology foundation models learn visual representations from whole-slide images (WSIs). However, existing foundation models are trained on disparate datasets with varying strategies, leading to inconsistent performance and limited generalizability. Here, we introduce ELF (Ensemble Learning of Foundation models), which integrates five pretrained pathology foundation models into unified slide-level representations. Trained on 53,699 WSIs spanning 20 anatomical sites, ELF leverages ensemble learning to capture complementary information across models. ELF’s slide-level architecture is designed for data-efficient downstream evaluation, including settings with limited data such as therapeutic response prediction. We evaluate ELF for disease classification and biomarker detection, as well as anticancer and immunotherapy response prediction across multiple cancer types. ELF achieves higher performance than the evaluated constituent and slide-level foundation models across the tested tasks, supporting further evaluation of ensemble learning for pathology applications in oncology.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"65 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148915157","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}
Cancer CellPub Date : 2026-09-10DOI: 10.1016/j.ccell.2026.08.013
Stefan Schulz,Sebastian Foersch
{"title":"Teamwork makes the dream work? Ensemble learning in computational pathology","authors":"Stefan Schulz,Sebastian Foersch","doi":"10.1016/j.ccell.2026.08.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.08.013","url":null,"abstract":"In this issue of Cancer Cell, Luo et al. report an ensemble approach that integrates five pretrained pathology foundation models into a slide-level representation to exploit their complementary information, yielding improvements in tumor subtyping, biomarker, and therapy-response prediction. This shows the potential of ensemble and multimodal approaches in computational pathology.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"58 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148915154","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":"UniCure: A multi-modal model for predicting personalized cancer therapy response","authors":"Zexi Chen,Saisai Tian,Jiazheng Pei,Ruichu Gu,Yongge Li,Shizhi Ding,Yaqian Xu,Xinlong Zheng,Miaoyu Liu,Xinxing Du,Yuanyuan Zhou,Junchao Zhu,Jiawei Zou,Jing Xu,Wenli Jiang,Chen Ye,Baijun Dong,Qi Zhang,Shengxiang Ren,Shu Wang,Han Wen,Weidong Zhang,Luonan Chen","doi":"10.1016/j.ccell.2026.07.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.07.010","url":null,"abstract":"Predicting drug efficacy across diverse patient contexts remains a major challenge in oncology, as models trained on cancer cell lines often fail to capture patient-specific biology. Emerging biological foundation models and patient-derived technologies offer a promising solution. Here, we present UniCure, a multi-modal model that combines biological and chemical foundation models to predict drug-induced transcriptomic responses across diverse cell and tissue contexts, enabling individualized drug ranking. Trained on 1.9 million transcriptomic perturbation profiles spanning >22,000 compounds, 166 cell types, and 24 tissues, UniCure accurately predicts dose-dependent and combination responses and generalizes across bulk and single-cell data. We further fine-tune UniCure on 345 patient-derived tumor-like cluster (PTC) transcriptomic profiles and validate performance on 396 real-world clinical profiles, demonstrating effective patient-level prediction. The model supports response-based patient stratification and is experimentally validated in cell line and patient-derived models. Overall, UniCure provides a practical framework for translating preclinical data into personalized therapeutic strategies.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"186 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908800","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}
Cancer CellPub Date : 2026-09-05DOI: 10.1016/j.ccell.2026.09.003
Claire Vennin,Chiara M. Cattaneo,Leontien Bosch,Serena Vegna,Xuhui Ma,Hugo G.J. Damstra,Moreno Martinovic,Efi Tsouri,Mila Ilic,Leyla Azarang,Jan R.T. van Weering,Emilia Pulver,Amber L. Zeeman,Tim Schelfhorst,Jeroen O. Lohuis,Anne C. Rios,Johanna F. Dekkers,Leila Akkari,Renee Menezes,Rene Medema,Serena R. Baglio,Anna Akhmanova,Sabine C. Linn,Simone Lemeer,Dirk M. Pegtel,Emile E. Voest,Jacco van Rheenen
{"title":"Retraction Notice to: Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity","authors":"Claire Vennin,Chiara M. Cattaneo,Leontien Bosch,Serena Vegna,Xuhui Ma,Hugo G.J. Damstra,Moreno Martinovic,Efi Tsouri,Mila Ilic,Leyla Azarang,Jan R.T. van Weering,Emilia Pulver,Amber L. Zeeman,Tim Schelfhorst,Jeroen O. Lohuis,Anne C. Rios,Johanna F. Dekkers,Leila Akkari,Renee Menezes,Rene Medema,Serena R. Baglio,Anna Akhmanova,Sabine C. Linn,Simone Lemeer,Dirk M. Pegtel,Emile E. Voest,Jacco van Rheenen","doi":"10.1016/j.ccell.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2026.09.003","url":null,"abstract":"","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"38 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893387","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}
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