Cancer Cell最新文献

英文中文

Circulating tumor DNA as a biomarker in early phase clinical trials 循环肿瘤DNA作为早期临床试验的生物标志物

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-19 DOI: 10.1016/j.ccell.2025.11.011

Harold N. Tan, Mitchell J. Elliott, Ian M. Silverman, Lillian L. Siu, Timothy A. Yap

引用次数: 0

Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence 人类胶质瘤从诊断到治疗和复发的多组学研究

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-11 DOI: 10.1016/j.ccell.2025.11.006

Hadeesha Piyadasa, Benjamin Oberlton, Mikaela Ribi, Ke Leow, Jolene S. Ranek, Inna Averbukh, Meelad Amouzgar, Candace C. Liu, Davide G. Franchina, Noah F. Greenwald, Erin F. McCaffrey, Rashmi Kumar, Selena Ferrian, Albert G. Tsai, Ferda Filiz, Christine Camacho Fullaway, Marc Bosse, Sricharan Reddy Varra, Alex Kong, Cameron Sowers, Michael Angelo

Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) landscape, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma, while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Paired samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206⁺ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study offers a framework for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

胶质瘤是最致命的癌症之一，治疗选择有限。为了揭示治疗逃逸和肿瘤微环境（TME）景观的特征，我们应用空间蛋白质组学、转录组学和糖组学对310名成人和儿童患者的670个病变进行了研究。单细胞分析显示，B7H3+肿瘤细胞在胶质母细胞瘤（GBM）和多形性黄色星形细胞瘤中的患病率很高，而大多数胶质瘤，包括儿科病例，在不到50%的肿瘤细胞中表达可靶向的肿瘤抗原，这可能解释了试验失败的原因。异柠檬酸脱氢酶（IDH）突变胶质瘤的成对样本揭示了肿瘤免疫空间重组驱动的复发，从T细胞和血管相关的骨髓细胞富集壁龛转移到小胶质细胞和CD206+巨噬细胞主导的肿瘤。多组学整合鉴定n -糖基化是最好的分级器，而免疫转录组最能预测GBM的生存。作为一种社区资源，本研究为胶质瘤的靶向、分类、结果预测和所有阶段TME组成的基线提供了一个框架。

{"title":"Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence","authors":"Hadeesha Piyadasa, Benjamin Oberlton, Mikaela Ribi, Ke Leow, Jolene S. Ranek, Inna Averbukh, Meelad Amouzgar, Candace C. Liu, Davide G. Franchina, Noah F. Greenwald, Erin F. McCaffrey, Rashmi Kumar, Selena Ferrian, Albert G. Tsai, Ferda Filiz, Christine Camacho Fullaway, Marc Bosse, Sricharan Reddy Varra, Alex Kong, Cameron Sowers, Michael Angelo","doi":"10.1016/j.ccell.2025.11.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.11.006","url":null,"abstract":"Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) landscape, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma, while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Paired samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study offers a framework for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"19 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717908","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

Oncofetal reprogramming of malignant seeds and their ecosystem: Implications in clinical research 恶性种子的癌胎重编程及其生态系统：在临床研究中的意义

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-11 DOI: 10.1016/j.ccell.2025.11.010

Ankur Sharma, Mehak Gupta, Jacob George, Florent Ginhoux

引用次数: 0

IL-36γ armored CAR T cells reprogram neutrophils to induce endogenous antitumor immunity IL-36γ装甲CAR - T细胞重编程中性粒细胞诱导内源性抗肿瘤免疫

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-11 DOI: 10.1016/j.ccell.2025.11.007

Yihan Zuo, David J. Vohwinkel, Bowen Dong, James R. McDowell, Brandon V. Guzman, Tharuna Sri Manickavel Pandian, Saborni Chattopadhyay, A.J.R. McGray, Scott H. Olejniczak, Joyce Ohm, Jianmin Wang, Mark D. Long, Eduardo Cortes Gomez, Terence J. Purdon, Wei Luo, Hemn Mohammadpour, Christopher S. Hackett, Leonid Cherkassky, Marco Davila, Scott I. Abrams, Renier J. Brentjens

Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors due to obstacles of antigen heterogeneity and the immunosuppressive tumor microenvironment (TME). Previous efforts focused on enhancing cytotoxicity and persistence of CAR T cells, while the feasibility of improving their therapeutic efficacy by leveraging the modulatory effects of CAR T cells on host anti-tumor immunity remains unclear. Here, we report that IL-36γ armored CAR T cells eradicate primary solid tumors and enable rejection of rechallenged antigen-negative tumors. IL-36γ armored CAR T cells favorably modulate the TME and reprogram unique neutrophil subsets with tumoricidal ability and antigen-(cross) presenting functions, resulting in the induction of endogenous T cells recognizing tumor antigens beyond CAR-targeted antigens. Our study demonstrates that neutrophil engagement by CAR T cells is a critical step in the establishment of the cancer-immunity cycle and introduces a broadly applicable method to overcome key barriers to adoptive cell therapies for solid tumors.

嵌合抗原受体（CAR） T细胞由于抗原异质性和免疫抑制肿瘤微环境（TME）的障碍，对实体肿瘤无效。以往的研究主要集中在增强CAR - T细胞的细胞毒性和持久性，而利用CAR - T细胞对宿主抗肿瘤免疫的调节作用来提高其治疗效果的可行性尚不清楚。在这里，我们报告IL-36γ装甲CAR - T细胞根除原发性实体瘤，并使抗原阴性肿瘤的再挑战排斥。IL-36γ装甲CAR- T细胞有利地调节TME和重编程独特的具有肿瘤杀伤能力和抗原（交叉）呈递功能的中性粒细胞亚群，导致诱导内源性T细胞识别肿瘤抗原，而不是CAR靶向抗原。我们的研究表明，CAR - T细胞与中性粒细胞的结合是建立癌症免疫周期的关键步骤，并引入了一种广泛适用的方法来克服实体瘤过继细胞治疗的关键障碍。

{"title":"IL-36γ armored CAR T cells reprogram neutrophils to induce endogenous antitumor immunity","authors":"Yihan Zuo, David J. Vohwinkel, Bowen Dong, James R. McDowell, Brandon V. Guzman, Tharuna Sri Manickavel Pandian, Saborni Chattopadhyay, A.J.R. McGray, Scott H. Olejniczak, Joyce Ohm, Jianmin Wang, Mark D. Long, Eduardo Cortes Gomez, Terence J. Purdon, Wei Luo, Hemn Mohammadpour, Christopher S. Hackett, Leonid Cherkassky, Marco Davila, Scott I. Abrams, Renier J. Brentjens","doi":"10.1016/j.ccell.2025.11.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.11.007","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors due to obstacles of antigen heterogeneity and the immunosuppressive tumor microenvironment (TME). Previous efforts focused on enhancing cytotoxicity and persistence of CAR T cells, while the feasibility of improving their therapeutic efficacy by leveraging the modulatory effects of CAR T cells on host anti-tumor immunity remains unclear. Here, we report that IL-36γ armored CAR T cells eradicate primary solid tumors and enable rejection of rechallenged antigen-negative tumors. IL-36γ armored CAR T cells favorably modulate the TME and reprogram unique neutrophil subsets with tumoricidal ability and antigen-(cross) presenting functions, resulting in the induction of endogenous T cells recognizing tumor antigens beyond CAR-targeted antigens. Our study demonstrates that neutrophil engagement by CAR T cells is a critical step in the establishment of the cancer-immunity cycle and introduces a broadly applicable method to overcome key barriers to adoptive cell therapies for solid tumors.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"3 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729188","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

Mapping the inflammatory origins of lung cancer 绘制肺癌炎症起源图

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-11 DOI: 10.1016/j.ccell.2025.11.005

Nobunari Sasaki, Mizuki Homme, Shunsuke Kitajima

How early precursor cells and their surrounding microenvironment cooperate to drive oncogenic progression in lung adenocarcinoma (LUAD) remains elusive. In this issue of Cancer Cell, Peng et al. conducted multimodal spatial-omics to comprehensively profile precancerous lung and LUAD tissues, uncovering alveolar progenitors and proinflammatory niches that co-evolve during cancer progression.

早期前体细胞及其周围微环境如何协同驱动肺腺癌（LUAD）的致癌进展仍然是一个谜。在这一期的Cancer Cell中，Peng等人通过多模态空间组学全面分析了癌前肺和LUAD组织，揭示了在癌症进展过程中共同进化的肺泡祖细胞和促炎利基。

引用次数: 0

TROP-2-targeted antibody-drug conjugate SHR-A1921 for advanced or metastatic solid tumors: A first-in-human phase 1 study. trop -2靶向抗体-药物偶联物shrr - a1921用于晚期或转移性实体瘤：一项首次人体i期研究

IF 44.5 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-08 Epub Date: 2025-10-23 DOI: 10.1016/j.ccell.2025.09.012

Jia Zhong, Lin Wu, Zhengbo Song, Nianzeng Xing, Jiujie Cui, Xingya Li, Kailun Fei, Dihong Tang, Qi Dang, Liang Chen, Tianshu Liu, Caigang Liu, Yong Li, Shichuan Zhang, Xinghua Han, Juxiang Xiao, Feng Guo, Min Yan, Huiting Xu, Chunxiu Yuan, Jincai Zhong, Rongrui Liu, Xiujuan Qu, Shikai Wu, Shusuan Jiang, Yan Yang, Panpan Zhang, Hongqian Guo, Ce Wang, Qiushi Xie, Zhifei Lin, Shuni Wang, Jie Wang

This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5-6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6-29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.

该研究是一项首次在人体内进行的三期i期试验（NCT05154604），旨在评估391例预先治疗的晚期/转移性实体瘤患者的TROP-2靶向抗体-药物偶联物SHR-A1921 （1.5-6.0 mg/kg / 3周）。132例患者（33.8%）发生≥3级治疗相关不良事件，最常见的是口腔炎，57例患者（14.6%）。SHR-A1921的血液学毒性发生率较低，只有3.1%的患者出现中性粒细胞计数≥3级下降。总体客观缓解率为24.8%(95%可信区间[CI]， 20.6-29.4)，在铂耐药卵巢癌、三阴性乳腺癌、小细胞肺癌、非小细胞肺癌、激素受体阳性乳腺癌、宫颈癌和胆道癌的队列中，总体客观缓解率为18.2% - 43.1%。TROP-2表达与治疗效果无显著相关性。总之，shrr - a1921表现出有希望的抗肿瘤活性和可管理的安全性，每3周3.0 mg/kg被选择用于进一步的临床开发。

{"title":"TROP-2-targeted antibody-drug conjugate SHR-A1921 for advanced or metastatic solid tumors: A first-in-human phase 1 study.","authors":"Jia Zhong, Lin Wu, Zhengbo Song, Nianzeng Xing, Jiujie Cui, Xingya Li, Kailun Fei, Dihong Tang, Qi Dang, Liang Chen, Tianshu Liu, Caigang Liu, Yong Li, Shichuan Zhang, Xinghua Han, Juxiang Xiao, Feng Guo, Min Yan, Huiting Xu, Chunxiu Yuan, Jincai Zhong, Rongrui Liu, Xiujuan Qu, Shikai Wu, Shusuan Jiang, Yan Yang, Panpan Zhang, Hongqian Guo, Ce Wang, Qiushi Xie, Zhifei Lin, Shuni Wang, Jie Wang","doi":"10.1016/j.ccell.2025.09.012","DOIUrl":"10.1016/j.ccell.2025.09.012","url":null,"abstract":"This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5-6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6-29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":" ","pages":"2268-2281.e3"},"PeriodicalIF":44.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367617","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

Functional pseudo-synapses: A new nexus in extracranial cancer. 功能性伪突触：颅外癌的新联系。

IF 44.5 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-08 Epub Date: 2025-10-23 DOI: 10.1016/j.ccell.2025.10.001

Xiaofei Zhi, Puran Zhang, Timothy C Wang

Functional cancer-to-neuron synapse-like connections are recognized as essential structures and hallmarks of both intracranial and extracranial tumors. In this issue of Cancer Cell, Ren et al. present high-resolution EM structures of pseudo-synaptic connections between sensory nerves and pancreatic ductal adenocarcinoma (PDAC).

功能性肿瘤与神经元突触样连接被认为是颅内和颅外肿瘤的基本结构和标志。在这一期的Cancer Cell中，Ren等人展示了感觉神经与胰腺导管腺癌（pancreatic ductal adencarcinoma， PDAC）之间伪突触连接的高分辨率EM结构。

引用次数: 0

Tumor-initiating stem cells engineer immunity 肿瘤启动干细胞工程免疫

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-04 DOI: 10.1016/j.ccell.2025.10.012

Zhe Yang, Linheng Li

Immunotherapy reshapes the interaction between the tumor microenvironment and cancer stem cells. In this issue of Cancer Cell, Guo et al. revealed that SOX2^High tumor-initiating stem cells reprogram neutrophils that block interferon-induced reprogramming after immunotherapy, maintaining their pro-tumor phenotype at the tumor-stroma interface.

免疫疗法重塑了肿瘤微环境与肿瘤干细胞之间的相互作用。在这一期的Cancer Cell中，Guo等人揭示了SOX2High肿瘤启动干细胞在免疫治疗后对中性粒细胞进行重编程，阻断干扰素诱导的重编程，在肿瘤-基质界面维持其促肿瘤表型。

引用次数: 0

A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma 一项纵向单细胞图谱预测bcma定向CAR - T细胞治疗多发性骨髓瘤后的预后和毒性

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-04 DOI: 10.1016/j.ccell.2025.10.014

Michael Rade, David Fandrei, Markus Kreuz, Sabine Seiffert, Anja Grahnert, Maik Friedrich, Thomas Wiemers, Patrick Born, Luise Fischer, Heike Weidner, Lorenz C. Hofbauer, Ronny Baber, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Jonathan Scolnick, Mirco Friedrich, Farid Keramati, Peter Brazda, Zsolt Sebestyen, Maximilian Merz

Chimeric antigen receptor (CAR) T cell therapies targeting B cell maturation antigen (BCMA) are transforming treatment for relapsed or refractory multiple myeloma (RRMM). We analyze 61 RRMM patients receiving idecabtagene vicleucel (Ide-cel; n = 34) or ciltacabtagene autoleucel (Cilta-cel; n = 27) and find that Cilta-cel achieves higher complete response (CR) rates (78% vs. 38%) and longer progression-free survival. Using a longitudinal single-cell multi-omics atlas of 135 blood samples, we show that Cilta-cel induces expansion of CD4⁺ cytotoxic T cells associated with CR and immune-related toxicities, whereas non-CR CD8⁺ T cells display impaired effector programs. Among non-B cells, plasmacytoid dendritic cells (pDCs) show the highest BCMA expression and BCMA-targeted agents eradicate a blastic plasmacytoid dendritic cell neoplasm line, suggesting a novel therapeutic avenue for this disease. Greater reductions in soluble BCMA correlate with enhanced CAR T expansion and systemic inflammation. These findings reveal cellular mechanisms driving differential efficacy and toxicity of BCMA-directed immunotherapy.

靶向B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR） T细胞疗法正在改变复发或难治性多发性骨髓瘤（RRMM）的治疗方法。我们分析了61例接受idecabtagene vicleucel （Ide-cel, n = 34）或ciltacabtagene autotoleucel （Cilta-cel, n = 27）治疗的RRMM患者，发现Cilta-cel获得了更高的完全缓解（CR）率（78%对38%）和更长的无进展生存期。利用135份血液样本的纵向单细胞多组学图谱，我们发现cilta -cell诱导与CR和免疫相关毒性相关的CD4+细胞毒性T细胞扩增，而非CR CD8+ T细胞显示受损的效应程序。在非b细胞中，浆细胞样树突状细胞（pDCs）显示出最高的BCMA表达，BCMA靶向药物可根除母细胞浆细胞样树突状肿瘤系，为该疾病的治疗提供了新的途径。可溶性BCMA的减少与CAR - T扩增和全身性炎症相关。这些发现揭示了驱动bcma定向免疫治疗差异疗效和毒性的细胞机制。

{"title":"A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma","authors":"Michael Rade, David Fandrei, Markus Kreuz, Sabine Seiffert, Anja Grahnert, Maik Friedrich, Thomas Wiemers, Patrick Born, Luise Fischer, Heike Weidner, Lorenz C. Hofbauer, Ronny Baber, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Jonathan Scolnick, Mirco Friedrich, Farid Keramati, Peter Brazda, Zsolt Sebestyen, Maximilian Merz","doi":"10.1016/j.ccell.2025.10.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.10.014","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapies targeting B cell maturation antigen (BCMA) are transforming treatment for relapsed or refractory multiple myeloma (RRMM). We analyze 61 RRMM patients receiving idecabtagene vicleucel (Ide-cel; n = 34) or ciltacabtagene autoleucel (Cilta-cel; n = 27) and find that Cilta-cel achieves higher complete response (CR) rates (78% vs. 38%) and longer progression-free survival. Using a longitudinal single-cell multi-omics atlas of 135 blood samples, we show that Cilta-cel induces expansion of CD4+ cytotoxic T cells associated with CR and immune-related toxicities, whereas non-CR CD8+ T cells display impaired effector programs. Among non-B cells, plasmacytoid dendritic cells (pDCs) show the highest BCMA expression and BCMA-targeted agents eradicate a blastic plasmacytoid dendritic cell neoplasm line, suggesting a novel therapeutic avenue for this disease. Greater reductions in soluble BCMA correlate with enhanced CAR T expansion and systemic inflammation. These findings reveal cellular mechanisms driving differential efficacy and toxicity of BCMA-directed immunotherapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"7 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664472","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

Precision treatment with artificial intelligence assisted subtyping enhances therapeutic efficacy in HR+/HER2− breast cancer: The LINUXtrial 人工智能辅助亚型分型的精准治疗可提高HR+/HER2−乳腺癌的治疗效果：LINUXtrial

IF 50.3 1区医学 Q1 CELL BIOLOGY

Cancer Cell

Pub Date : 2025-12-04 DOI: 10.1016/j.ccell.2025.11.003

Lei Fan, Wen-Juan Zhang, Hui-Ping Li, Xiao-Hua Zeng, Yue-E Teng, Yue Gong, Xi Jin, Shen Zhao, Tao Sun, Wen-Yan Chen, Shu-Sen Wang, Jin Yang, Zhi-Gang Zhuang, Su-Jie Ni, Zhi-Xian He, De-Yuan Fu, Chuan-Gui Song, Zheng Lv, Qian-Nan Liang, Bao-Hua Yu, Zhi-Ming Shao

We report the results of LINUX (NCT05594095), a multicenter, randomized, controlled phase II platform trial aiming to identify effective precision treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer after resistance to cyclin-dependent kinase 4/6 inhibitor. A total of 105 patients were categorized into four similarity network fusion (SNF) subtypes by artificial intelligence-assisted classification and randomly assigned to receive subtyping-based precision therapy (N = 70) or treatment of physician’s choice (N = 35). Results demonstrate superior primary endpoint of objective response rates in the subtyping-based groups compared to controls: 10% versus 0% for SNF1, 65% versus 30% for SNF2, 40% versus 30% for SNF3, and 70% versus 20% for SNF4. Grade 3–4 treatment-related adverse events occurred in 37% of both groups. These findings highlight the clinical benefits of subtyping-based precision therapies, particularly for SNF2 and SNF4 subtypes, warranting further validation in phase III trials.

我们报告了LINUX （NCT05594095）的结果，这是一项多中心、随机、对照的II期平台试验，旨在确定激素受体阳性/人表皮生长因子受体2阴性转移性乳腺癌对细胞周期蛋白依赖性激酶4/6抑制剂耐药后的有效精确治疗方法。通过人工智能辅助分类将105例患者分为4个相似网络融合（SNF）亚型，随机分配接受基于亚型的精准治疗（N = 70）或医生选择治疗（N = 35）。结果显示，与对照组相比，基于亚型的组的客观缓解率的主要终点优于对照组：SNF1为10%对0%，SNF2为65%对30%，SNF3为40%对30%，SNF4为70%对20%。3-4级治疗相关不良事件发生率在两组中均为37%。这些发现强调了基于亚型的精确治疗的临床益处，特别是针对SNF2和SNF4亚型，需要在III期试验中进一步验证。

{"title":"Precision treatment with artificial intelligence assisted subtyping enhances therapeutic efficacy in HR+/HER2− breast cancer: The LINUXtrial","authors":"Lei Fan, Wen-Juan Zhang, Hui-Ping Li, Xiao-Hua Zeng, Yue-E Teng, Yue Gong, Xi Jin, Shen Zhao, Tao Sun, Wen-Yan Chen, Shu-Sen Wang, Jin Yang, Zhi-Gang Zhuang, Su-Jie Ni, Zhi-Xian He, De-Yuan Fu, Chuan-Gui Song, Zheng Lv, Qian-Nan Liang, Bao-Hua Yu, Zhi-Ming Shao","doi":"10.1016/j.ccell.2025.11.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.11.003","url":null,"abstract":"We report the results of LINUX (NCT05594095<svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg>), a multicenter, randomized, controlled phase II platform trial aiming to identify effective precision treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer after resistance to cyclin-dependent kinase 4/6 inhibitor. A total of 105 patients were categorized into four similarity network fusion (SNF) subtypes by artificial intelligence-assisted classification and randomly assigned to receive subtyping-based precision therapy (N = 70) or treatment of physician’s choice (N = 35). Results demonstrate superior primary endpoint of objective response rates in the subtyping-based groups compared to controls: 10% versus 0% for SNF1, 65% versus 30% for SNF2, 40% versus 30% for SNF3, and 70% versus 20% for SNF4. Grade 3–4 treatment-related adverse events occurred in 37% of both groups. These findings highlight the clinical benefits of subtyping-based precision therapies, particularly for SNF2 and SNF4 subtypes, warranting further validation in phase III trials.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"12 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673659","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

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Cancer Cell

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀