Nature cancer最新文献_第8页

An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma. 原位工程嵌合IL-2受体增强了肾细胞癌中促炎CAR巨噬细胞的杀瘤活性。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 Epub Date: 2025-04-29 DOI: 10.1038/s43018-025-00950-1

Weiqiang Jing, Maosen Han, Ganyu Wang, Zhichao Kong, Xiaotian Zhao, Zhipeng Fu, Xuewen Jiang, Chongdeng Shi, Chen Chen, Jing Zhang, Zuolin Zheng, Jinxin Gao, Weiyi Sun, Chunwei Tang, Zhenmei Yang, Yan Wang, Ying Liu, Kun Zhao, Danqing Zhu, Benkang Shi, Xinyi Jiang

{"title":"An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma.","authors":"Weiqiang Jing, Maosen Han, Ganyu Wang, Zhichao Kong, Xiaotian Zhao, Zhipeng Fu, Xuewen Jiang, Chongdeng Shi, Chen Chen, Jing Zhang, Zuolin Zheng, Jinxin Gao, Weiyi Sun, Chunwei Tang, Zhenmei Yang, Yan Wang, Ying Liu, Kun Zhao, Danqing Zhu, Benkang Shi, Xinyi Jiang","doi":"10.1038/s43018-025-00950-1","DOIUrl":"10.1038/s43018-025-00950-1","url":null,"abstract":"Chimeric antigen receptor macrophage (CAR-M) therapy has shown great promise in solid malignancies; however, the phenotypic re-domestication of CAR-Ms in the immunosuppressive tumor niche restricts their antitumor immunity. We here report an in situ engineered chimeric interleukin (IL)-2 signaling receptor (CSR) for controllably manipulating the proinflammatory phenotype of CAR-Ms, augmenting their sustained tumoricidal immunity. Specifically, our in-house-customized lipid nanoparticles efficiently introduce dual circular RNAs into macrophages to generate CSR-functionalized CAR-Ms. The intracellular inflammatory signaling pathway of CAR-Ms can be stimulated with the IL-2 therapeutic via the synthetic IL-2 receptor, which induces the antitumor phenotype shifting of CAR-Ms. Moreover, hydrogel-mediated combinatory treatment with lipid nanoparticles and IL-2 remodels the immunosuppressive tumor microenvironment and promotes tumor regression in renal carcinoma animal models. In summary, our findings establish that the proinflammatory phenotype of CAR-Ms can be modulated by a synthetic IL-2 receptor, benefiting the antitumor immunotherapy of CAR-Ms with broad application in other solid malignancies.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"838-853"},"PeriodicalIF":23.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028848","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

Palmitoylation regulates ferroptosis and anti-tumor immunity. 棕榈酰化调节铁下垂和抗肿瘤免疫。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 DOI: 10.1038/s43018-025-00972-9

Robin Demuynck, Mariia Saviuk, Dmitri V Krysko

引用次数: 0

CHD1 status drives divergent metabolic pathways in SPOP-mutant prostate cancer. spop突变前列腺癌中CHD1状态驱动不同的代谢途径。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 DOI: 10.1038/s43018-025-00959-6

Jacob J Orme, Emmanuel S Antonarakis, Scott M Dehm

引用次数: 0

Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma. 食管癌新辅助治疗中的进化和免疫微环境动力学。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 Epub Date: 2025-05-14 DOI: 10.1038/s43018-025-00955-w

Melissa Barroux, Jacob Househam, Eszter Lakatos, Tahel Ronel, Ann-Marie Baker, Henrike Salié, Maximilian Mossner, Kane Smith, Chris Kimberley, Salpie Nowinski, Alison Berner, Vinaya Gunasri, Martin Borgmann, Sven Liffers, Marnix Jansen, Giulio Caravagna, Katja Steiger, Julia Slotta-Huspenina, Wilko Weichert, Luis Zapata, Eleftheria Giota, Sylvie Lorenzen, Markus Alberstmeier, Benny Chain, Helmut Friess, Bertram Bengsch, Roland M Schmid, Jens T Siveke, Michael Quante, Trevor A Graham

{"title":"Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma.","authors":"Melissa Barroux, Jacob Househam, Eszter Lakatos, Tahel Ronel, Ann-Marie Baker, Henrike Salié, Maximilian Mossner, Kane Smith, Chris Kimberley, Salpie Nowinski, Alison Berner, Vinaya Gunasri, Martin Borgmann, Sven Liffers, Marnix Jansen, Giulio Caravagna, Katja Steiger, Julia Slotta-Huspenina, Wilko Weichert, Luis Zapata, Eleftheria Giota, Sylvie Lorenzen, Markus Alberstmeier, Benny Chain, Helmut Friess, Bertram Bengsch, Roland M Schmid, Jens T Siveke, Michael Quante, Trevor A Graham","doi":"10.1038/s43018-025-00955-w","DOIUrl":"10.1038/s43018-025-00955-w","url":null,"abstract":"Locally advanced esophageal adenocarcinoma remains difficult to treat and the ecological and evolutionary dynamics responsible for resistance and recurrence are incompletely understood. Here, we performed longitudinal multiomic analysis of patients with esophageal adenocarcinoma in the MEMORI trial. Multi-region multi-timepoint whole-exome and paired transcriptome sequencing was performed on 27 patients before, during and after neoadjuvant treatment. We found major transcriptomic changes during treatment with upregulation of immune, stromal and oncogenic pathways. Genetic data revealed that clonal sweeps through treatment were rare. Imaging mass cytometry and T cell receptor sequencing revealed remodeling of the tumor microenvironment during treatment. The presence of genetic immune escape, a less-cytotoxic T cell phenotype and a lack of clonal T cell expansions were linked to poor treatment response. In summary, there were widespread transcriptional and environmental changes through treatment, with limited clonal replacement, suggestive of phenotypic plasticity.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"820-837"},"PeriodicalIF":23.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079240","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}

引用次数: 0

Classifying InDel signatures in tumors. 肿瘤中InDel信号的分类。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 DOI: 10.1038/s43018-025-00999-y

Tiffanie Chouleur

引用次数: 0

CHD1 loss reprograms SREBP2-driven cholesterol synthesis to fuel androgen-responsive growth and castration resistance in SPOP-mutated prostate tumors. CHD1缺失重编程srebp2驱动的胆固醇合成，在spop突变的前列腺肿瘤中促进雄激素响应性生长和去势抵抗。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 Epub Date: 2025-05-13 DOI: 10.1038/s43018-025-00952-z

Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao

{"title":"CHD1 loss reprograms SREBP2-driven cholesterol synthesis to fuel androgen-responsive growth and castration resistance in SPOP-mutated prostate tumors.","authors":"Feiyu Chen, Haoyan Li, Yin Wang, Ximing Tang, Kevin Lin, Qidong Li, Chenling Meng, Wei Shi, Javier Leo, Xin Liang, Jie Zhang, Vivien Van, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Maria G Raso, Ana Aparicio, Yue Lu, Daniel E Frigo, Boyi Gan, Di Zhao","doi":"10.1038/s43018-025-00952-z","DOIUrl":"10.1038/s43018-025-00952-z","url":null,"abstract":"Despite undergoing castration, most individuals with prostate cancer (PCa) experience progression to castration-resistant PCa (CRPC), in which the androgen receptor (AR) remains an important driver. Concurrent genetic alterations in SPOP and CHD1 define a unique subtype of PCa, but their interactions in tumor progression and therapy response remain unclear. Here, we provide genetic evidence supporting that CHD1 loss accelerates disease progression and confers resistance to castration in males with SPOP-mutated PCa. By leveraging genetic engineering and multiomics, we uncovered a noncanonical function of CHD1 in lipid metabolism reprogramming via repressing the SREBP2 transcriptome. Loss of CHD1 induces cholesterol production, supplies intratumoral androgen biosynthesis and enhances AR activity, leading to castration resistance of SPOP-mutated PCa. Combining anti-androgen therapy with cholesterol-lowering drugs showed synergistic and durable activity against CRPC harboring CHD1 loss and SPOP mutations. These findings advance our understanding of an emerging PCa subtype and offer biomarker-driven combinatorial treatment strategies for men with CRPC.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"854-873"},"PeriodicalIF":23.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005998","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}

引用次数: 0

Resistance to TIL therapy in lung cancer mediated by clonal T cell loss and neoantigen escape. 克隆T细胞丢失和新抗原逃逸介导的肺癌对TIL治疗的耐药性。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 DOI: 10.1038/s43018-025-00947-w

引用次数: 0

UnitedMet harnesses RNA-metabolite covariation to impute metabolite levels in clinical samples. UnitedMet利用rna -代谢物共变来估算临床样品中的代谢物水平。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 Epub Date: 2025-04-18 DOI: 10.1038/s43018-025-00943-0

Amy X Xie, Wesley Tansey, Ed Reznik

{"title":"UnitedMet harnesses RNA-metabolite covariation to impute metabolite levels in clinical samples.","authors":"Amy X Xie, Wesley Tansey, Ed Reznik","doi":"10.1038/s43018-025-00943-0","DOIUrl":"10.1038/s43018-025-00943-0","url":null,"abstract":"Comprehensively studying metabolism requires metabolite measurements. Such measurements, however, are often unavailable in large cohorts of tissue samples. To address this basic barrier, we propose a Bayesian framework ('UnitedMet') that leverages RNA-metabolite covariation to impute otherwise unmeasured metabolite levels from widely available transcriptomic data. UnitedMet is equally capable of imputing whole pool sizes and outcomes of isotope tracing experiments. We apply UnitedMet to investigate the metabolic impact of driver mutations in kidney cancer, identifying an association between BAP1 and a highly oxidative tumor phenotype. We similarly apply UnitedMet to determine that advanced kidney cancers upregulate oxidative phosphorylation relative to early-stage disease, that oxidative metabolism in kidney cancer is associated with inferior outcomes to anti-angiogenic therapy and that kidney cancer metastases demonstrate elevated oxidative phosphorylation. UnitedMet provides a scalable tool for assessing metabolic phenotypes when direct measurements are infeasible, facilitating unexplored avenues for metabolite-focused hypothesis generation.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"892-906"},"PeriodicalIF":23.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972501","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}

引用次数: 0

The diverse roles of the circadian clock in cancer. 生物钟在癌症中的多种作用。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 Epub Date: 2025-05-26 DOI: 10.1038/s43018-025-00981-8

Bridget M Fortin, Alisa L Mahieu, Rachel C Fellows, Yi Kang, Amber N Lewis, Aya S Ead, Katja A Lamia, Yin Cao, Nicholas R Pannunzio, Selma Masri

引用次数: 0

In vivo macrophage engineering for renal cancer therapy. 体内巨噬细胞工程用于肾癌治疗。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-05-01 DOI: 10.1038/s43018-025-00912-7

Débora Basílio-Queirós, Nico Lachmann

引用次数: 0