Cancer discovery最新文献_第5页

Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery 外周血是癌症新抗原和反应性t细胞发现的唯一来源

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-09-29 DOI: 10.1158/2159-8290.cd-25-1779

Andrea Garcia-Garijo, Immaculada Creus-González, Pierre L. Levy, Ana Belén Moreno-Cárdenas, Endika Prieto-Fernández, Maria Lozano-Rabella, Carlos Alberto Fajardo, Ricardo Pujol-Borrell, Albert Marín-Bayo, Johanna Kusnick, Jonatan Gonzalez, Carla Brujas, Jared J. Gartner, Anna Yuste-Estevanez, Alma M. Calahorro, Aya Louhamane, Jose Fernandez, Rebeca Sanz-Pamplona, Thomas B.K. Watkins, Vladimir Galvao, Eva Munoz-Couselo, Javier Ros, Elena Élez, Mafalda Oliveira, Cristina Saura Manich, Irene Brana, Ana Oaknin, Ramon Alemany, Josep Tabernero, Raquel Perez-Lopez, Simon Turcotte, Alexander M. Frankell, Elena Garralda, Rodrigo A. Toledo, Alena Gros

{"title":"Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery","authors":"Andrea Garcia-Garijo, Immaculada Creus-González, Pierre L. Levy, Ana Belén Moreno-Cárdenas, Endika Prieto-Fernández, Maria Lozano-Rabella, Carlos Alberto Fajardo, Ricardo Pujol-Borrell, Albert Marín-Bayo, Johanna Kusnick, Jonatan Gonzalez, Carla Brujas, Jared J. Gartner, Anna Yuste-Estevanez, Alma M. Calahorro, Aya Louhamane, Jose Fernandez, Rebeca Sanz-Pamplona, Thomas B.K. Watkins, Vladimir Galvao, Eva Munoz-Couselo, Javier Ros, Elena Élez, Mafalda Oliveira, Cristina Saura Manich, Irene Brana, Ana Oaknin, Ramon Alemany, Josep Tabernero, Raquel Perez-Lopez, Simon Turcotte, Alexander M. Frankell, Elena Garralda, Rodrigo A. Toledo, Alena Gros","doi":"10.1158/2159-8290.cd-25-1779","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-1779","url":null,"abstract":"Neoantigen-targeted T-cell therapies require invasive tumor biopsies to identify neoantigens and reactive T cells, limiting their applicability and potentially underestimating tumor heterogeneity. We propose a novel strategy relying solely on peripheral blood to identify non-synonymous mutations via cell-free DNA whole-exome sequencing and isolate neoantigen-specific CD4+ and CD8+ T cells based on PD-1 and CD39 co-expression. Our method identified most neoantigens and increased the number of T-cell reactivities detected by standard biopsy-based techniques in an initial cohort of eight metastatic cancer patients. Critically, our approach uncovered additional neoantigens missed by tumor biopsy analysis, highlighting the potential for broader neoantigen targeting using liquid biopsies. Analysis of a cohort of 69 metastatic cancer patients revealed that approximately half could be eligible for our blood-only approach. This proof-of-concept study demonstrates the potential of using blood as a surrogate or complement for tumor biopsies to develop neoantigen-reactive T-cell therapies against a broader spectrum of neoantigens.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"16 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070942","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}

引用次数: 0

Spatially confined IL-12 programs CAR-NK through mTORC1 to coordinate antitumor immune networks. 空间受限的IL-12通过mTORC1编程CAR-NK来协调抗肿瘤免疫网络。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-09-29 DOI: 10.1158/2159-8290.CD-26-0509

Mubin Tarannum, Khanhlinh Dinh, Mila Stanojevic, Maily Nguyen, Marco Campisi, Andreia Maia, Fuguo Liu, Shaobo Yang, Grace C Birch, Eden Bobilev, Ian Gillanders, Michal Sheffer, Shikha Gupta, Junning Wang, Suthakar Ganapathy, Daniel E Michaud, Guillermo Nicolas Dalton, Seema Chugh, Quang-De Nguyen, Cloud P Paweletz, Prafulla C Gokhale, Yang Gao, Jose Cancelas, Jennifer L Guerriero, Toni K Choueiri, David A Barbie, Andrew J Aguirre, Rebecca L Porter, Ursula A Matulonis, John Koreth, Catherine J Wu, Robert J Soiffer, Jerome Ritz, Jianzhu Chen, Rizwan Romee

{"title":"Spatially confined IL-12 programs CAR-NK through mTORC1 to coordinate antitumor immune networks.","authors":"Mubin Tarannum, Khanhlinh Dinh, Mila Stanojevic, Maily Nguyen, Marco Campisi, Andreia Maia, Fuguo Liu, Shaobo Yang, Grace C Birch, Eden Bobilev, Ian Gillanders, Michal Sheffer, Shikha Gupta, Junning Wang, Suthakar Ganapathy, Daniel E Michaud, Guillermo Nicolas Dalton, Seema Chugh, Quang-De Nguyen, Cloud P Paweletz, Prafulla C Gokhale, Yang Gao, Jose Cancelas, Jennifer L Guerriero, Toni K Choueiri, David A Barbie, Andrew J Aguirre, Rebecca L Porter, Ursula A Matulonis, John Koreth, Catherine J Wu, Robert J Soiffer, Jerome Ritz, Jianzhu Chen, Rizwan Romee","doi":"10.1158/2159-8290.CD-26-0509","DOIUrl":"10.1158/2159-8290.CD-26-0509","url":null,"abstract":"Solid tumors evade immunotherapy because of immunosuppressive microenvironments that limit immune cell persistence and function. Although interleukin-12 (IL-12) potently activates antitumor immunity, its clinical use has been constrained by systemic toxicity. Here we engineered a CAR natural killer (NK) cell platform that integrated IL-12 signaling to enhance antitumor immunity. IL-12 signaling synergized with CAR activation to sustain mTORC1 activity through convergent Ras-ERK and PI3K pathways, promoting metabolic fitness, autonomous expansion, and sustained effector function. IL-12 also activated bystander NK cells, T cells, and macrophages to remodel the tumor microenvironment. To improve safety, IL-12 was tethered to a collagen-binding A3-domain, restricting its activity to the extracellular matrix and limiting systemic exposure. In ovarian and pancreatic cancer models, matrix-anchored IL-12 CAR NK cells expanded without exogenous cytokines and achieved durable tumor control. These findings suggest that mTORC1-mediated integration of CAR and cytokine signaling can enhance immune fitness and overcome immunosuppressive tumor microenvironments.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079904","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}

引用次数: 0

Q&A: Eileen O’Reilly on Pancreatic Cancer 问答：艾琳·奥莱利谈胰腺癌

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-09-28 DOI: 10.1158/2159-8290.cd-nw2026-0092

引用次数: 0

Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion. 决定异体CAR - T细胞排斥和扩增的细胞和分子机制。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-09-25 DOI: 10.1158/2159-8290.CD-26-0248

Andrew P Jallouk, Zhongqi Ge, Vivek Kaimal, Kristen Zhang, Elvin J Lauron, Paul B Robbins, Zachary J Roberts, Emerie Danson, Matthew D Richard, Pragya Devashish, Sattva S Neelapu, Pavan Bachireddy

{"title":"Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.","authors":"Andrew P Jallouk, Zhongqi Ge, Vivek Kaimal, Kristen Zhang, Elvin J Lauron, Paul B Robbins, Zachary J Roberts, Emerie Danson, Matthew D Richard, Pragya Devashish, Sattva S Neelapu, Pavan Bachireddy","doi":"10.1158/2159-8290.CD-26-0248","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-26-0248","url":null,"abstract":"Allogeneic CAR T cells could overcome limitations of autologous therapies but are limited by immune rejection. We evaluated 11 patients with large B‑cell lymphoma treated with a single lot of cemacabtagene ansegedleucel (cema-cel), an allogeneic anti‑CD19 CAR T product. Despite receiving identical infusion products, patients exhibited heterogeneous cema-cel expansion and clinical outcomes. Our integrated analyses using longitudinal TCRβ sequencing, single‑cell molecular profiling, and mixed lymphocyte reaction assays revealed that high frequencies of pre‑existing, recipient-derived alloreactive CD8+ T cells mediated rapid CAR T rejection in non-expanders. Furthermore, effector-like features, rather than stem/central memory programs, drove robust clonal CAR T expansion consistently across expanders. We confirmed similar expansion patterns in two independent cohorts treated with a separate lot of cema-cel or an allogeneic anti-BCMA CAR T product. These findings highlight distinct cell‑extrinsic and cell‑intrinsic mechanisms that influence allogeneic CAR T performance and provide insights to optimize donor selection, manufacturing, and product design.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036469","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}

引用次数: 0

Microplastics and Cancer: Still Searching for Causation 微塑料和癌症：仍在寻找因果关系

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-09-24 DOI: 10.1158/2159-8290.cd-nw2026-0091

引用次数: 0

The liver niche accelerates, while the lung niche restrains secondary spread of breast cancer. 肝生态位加速了乳腺癌的扩散，而肺生态位抑制了乳腺癌的继发性扩散。

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-09-22 DOI: 10.1158/2159-8290.CD-25-1652

Magdalena K Sznurkowska, Francesc Castro-Giner, Irene D'Anna, Ilona Krol, Yongzhan Zhang, Lauren L Ozimski, Massimo Saini, Jianwen Zhou, Simran Asawa, David Gremmelspacher, Alexander Ring, Karin Strittmatter, Fabienne Dominique Schwab, Yu Wei Zhang, Selina Budinjas, Marko Vujanovic, Zacharias Kontarakis, Giada Pontecorvi, Francesca Albrecht, Kirsten D Mertz, Gaël Auray, Claudio Giachino, Verdon Taylor, Ana Gvozdenovic, Werner J Kovacs, Ilaria Malanchi, Heike Frauchiger-Heuer, Andreas Wicki, Marcus Vetter, Matteo Ligorio, Nicola Aceto

{"title":"The liver niche accelerates, while the lung niche restrains secondary spread of breast cancer.","authors":"Magdalena K Sznurkowska, Francesc Castro-Giner, Irene D'Anna, Ilona Krol, Yongzhan Zhang, Lauren L Ozimski, Massimo Saini, Jianwen Zhou, Simran Asawa, David Gremmelspacher, Alexander Ring, Karin Strittmatter, Fabienne Dominique Schwab, Yu Wei Zhang, Selina Budinjas, Marko Vujanovic, Zacharias Kontarakis, Giada Pontecorvi, Francesca Albrecht, Kirsten D Mertz, Gaël Auray, Claudio Giachino, Verdon Taylor, Ana Gvozdenovic, Werner J Kovacs, Ilaria Malanchi, Heike Frauchiger-Heuer, Andreas Wicki, Marcus Vetter, Matteo Ligorio, Nicola Aceto","doi":"10.1158/2159-8290.CD-25-1652","DOIUrl":"https://doi.org/10.1158/2159-8290.CD-25-1652","url":null,"abstract":"Breast cancer progression to visceral organs such as the lung and liver is associated with poor prognosis. Yet, these organs have diverse cellular microenvironments that may differentially influence cancer cell behavior. Here, we show that breast cancer metastases differ in their capacity for secondary seeding: the liver fosters metastasis-promoting properties and boosts secondary spread, whereas the lung restricts these processes, favoring local growth. Using patient data and rapid autopsy tissues, mouse models with barcode-mediated tracing, niche-labeling technology, and single-cell analysis of tumor cells and their direct microenvironment, we dissect the cellular and molecular microenvironmental factors underlying this differential behavior. Mechanistically, we identify BMP2-producing endothelial cells as critical players within the liver metastatic niche, enhancing metastasis-to-metastasis dissemination. Targeting the BMP2 signaling axis suppresses secondary spread of liver-derived breast cancer lesions. Altogether, we reveal site-specific behavior of lung and liver metastases in breast cancer, highlighting microenvironmental mechanisms and therapeutic opportunities for intervention.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":" ","pages":""},"PeriodicalIF":29.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015542","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}

引用次数: 0

Targeting RAS for Pancreatic Cancer Interception. 靶向RAS用于胰腺癌阻断

IF 29.5 1区医学

Cancer discovery Pub Date : 2026-09-22 DOI: 10.1158/2159-8290.CD-26-1179

Sandra Misale, Neeha Zaidi, Elizabeth M Jaffee, Alison P Klein, Laura D Wood

引用次数: 0

Phase III Trials Test First-Line Options in Advanced NSCLC III期临床试验测试晚期NSCLC一线治疗方案

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-09-18 DOI: 10.1158/2159-8290.cd-nw2026-0090

引用次数: 0

Dual Functions of B7-H3-MAPK Signaling Orchestrate Tumor Immunosuppression via Regulating the Plasticity of Myeloid-derived Suppressor Cells and Fibroblasts B7-H3-MAPK信号通过调节髓源性抑制细胞和成纤维细胞的可塑性调控肿瘤免疫抑制的双重功能

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-09-18 DOI: 10.1158/2159-8290.cd-25-1613

Wei Shi, Ping Xu, Qianlin Gu, Zhen Fan, Xin Liang, Yin Wang, Yuehui Zhao, Chenling Meng, Javier Leo, Justin J. Kim, Hongqi Teng, Jie Zhang, Feiyu Chen, Yang Chen, Nicholas E. Navin, Di Zhao

{"title":"Dual Functions of B7-H3-MAPK Signaling Orchestrate Tumor Immunosuppression via Regulating the Plasticity of Myeloid-derived Suppressor Cells and Fibroblasts","authors":"Wei Shi, Ping Xu, Qianlin Gu, Zhen Fan, Xin Liang, Yin Wang, Yuehui Zhao, Chenling Meng, Javier Leo, Justin J. Kim, Hongqi Teng, Jie Zhang, Feiyu Chen, Yang Chen, Nicholas E. Navin, Di Zhao","doi":"10.1158/2159-8290.cd-25-1613","DOIUrl":"https://doi.org/10.1158/2159-8290.cd-25-1613","url":null,"abstract":"B7-H3/CD276 is an emerging immunotherapy target in cancers. However, limited knowledge of B7-H3 signaling and its role in modulating the tumor microenvironment hinders the clinical application of B7-H3-targeting therapy. Here, we report that B7-H3 plays dual roles in regulating myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs), thereby promoting tumor progression and therapy resistance, respectively. We comprehensively characterized a non-canonical function of B7-H3 that triggers MAPK signaling in monocytic MDSCs and induces cellular senescence. The senescent monocytic M-MDSCs secreted chemokines to recruit immunosuppressive granulocytic MDSCs. Genetic deletion or pharmacological inhibition of B7-H3/Cd276 reduced Gr-MDSCs and delayed tumor progression. Nevertheless, the secretory factor SPINK1 derived from MDSCs compensatorily activates EGFR/MEK/ERK signaling in CAFs and promotes their extracellular matrix remodeling features, dampening B7-H3-targeting immunotherapy. Combining the B7-H3 monoclonal antibody with the FDA-approved MEK inhibitor trametinib showed durable anti-tumor effects in preclinical models of castration-resistant prostate cancer by fully attenuating immunosuppressive mechanisms.","PeriodicalId":9430,"journal":{"name":"Cancer discovery","volume":"17 1","pages":""},"PeriodicalIF":28.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148985101","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}

引用次数: 0

Anti–B7-H3 ADCs Take Center Stage against SCLC at WCLC 抗b7 - h3 adc在WCLC中对SCLC起中心作用

IF 28.2 1区医学

Cancer discovery Pub Date : 2026-09-17 DOI: 10.1158/2159-8290.cd-nw2026-0088

引用次数: 0