Nature cancer最新文献

Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer. 全外显子组肿瘤不可知ctDNA分析增强了最小残留疾病检测并揭示了局部结肠癌的复发机制。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-04-29 DOI: 10.1038/s43018-025-00960-z

Jorge Martín-Arana, Francisco Gimeno-Valiente, Tenna Vesterman Henriksen, Blanca García-Micó, Belén Martínez-Castedo, Valentina Gambardella, Carolina Martínez-Ciarpaglini, Brenda Palomar, Marisol Huerta, Daniel G Camblor, Miguel García Bartolomé, Juan Antonio Carbonell-Asins, Amanda Frydendahl, Kåre Andersson Gotchalck, Tania Fleitas, Roberto Tébar-Martínez, David Moro, Vicente Pla, Leticia Pérez-Santiago, José Martín-Arévalo, David Casado, Stephanie García-Botello, Alejandro Espí, Susana Roselló, Desamparados Roda, Claus Lindbjerg Andersen, Andrés Cervantes, Noelia Tarazona

{"title":"Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer.","authors":"Jorge Martín-Arana, Francisco Gimeno-Valiente, Tenna Vesterman Henriksen, Blanca García-Micó, Belén Martínez-Castedo, Valentina Gambardella, Carolina Martínez-Ciarpaglini, Brenda Palomar, Marisol Huerta, Daniel G Camblor, Miguel García Bartolomé, Juan Antonio Carbonell-Asins, Amanda Frydendahl, Kåre Andersson Gotchalck, Tania Fleitas, Roberto Tébar-Martínez, David Moro, Vicente Pla, Leticia Pérez-Santiago, José Martín-Arévalo, David Casado, Stephanie García-Botello, Alejandro Espí, Susana Roselló, Desamparados Roda, Claus Lindbjerg Andersen, Andrés Cervantes, Noelia Tarazona","doi":"10.1038/s43018-025-00960-z","DOIUrl":"https://doi.org/10.1038/s43018-025-00960-z","url":null,"abstract":"In stage 2-3 colon cancer (CC), postsurgery circulating tumor DNA (ctDNA) assessment is crucial for guiding adjuvant chemotherapy (ACT) decisions. While existing assays detect ctDNA and help identify high-risk persons with CC for recurrence, their limited sensitivity after surgery poses challenges in deciding on ACT. Additionally, a substantial portion of persons with CC fail to clear ctDNA after ACT, leading to recurrence. In this study, we performed whole-exome sequencing (WES) of ctDNA at different time points in participants with relapsed CC in two independent cohorts, alongside transcriptomic and proteomic analyses of metastases, to enhance comprehension of progression mechanisms. A plasma WES-based tumor-agnostic assay demonstrated higher sensitivity in detecting minimal residual disease (MRD) compared to current assays. Immune evasion appears to be the primary driver of progression in the localized CC setting, indicating the potential efficacy of immunotherapy for microsatellite stability in persons with CC. Organoid modeling further supports the promising potential of targeted therapy in eradicating MRD, surpassing conventional treatments.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982674","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

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 : 2025-04-18 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":"https://doi.org/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":""},"PeriodicalIF":23.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adoptively transferred tumor-specific IL-9-producing cytotoxic CD8⁺ T cells activate host CD4⁺ T cells to control tumors with antigen loss. 过继性转移肿瘤特异性产生il -9的细胞毒性CD8+ T细胞激活宿主CD4+ T细胞以控制抗原丢失的肿瘤。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-04-03 DOI: 10.1038/s43018-025-00935-0

Liuling Xiao, Rui Duan, Wendao Liu, Chuanchao Zhang, Xingzhe Ma, Miao Xian, Qiang Wang, Qi Guo, Wei Xiong, Pan Su, Lingqun Ye, Yabo Li, Ling Zhong, Jianfei Qian, Yong Lu, Zhongming Zhao, Qing Yi

{"title":"Adoptively transferred tumor-specific IL-9-producing cytotoxic CD8+ T cells activate host CD4+ T cells to control tumors with antigen loss.","authors":"Liuling Xiao, Rui Duan, Wendao Liu, Chuanchao Zhang, Xingzhe Ma, Miao Xian, Qiang Wang, Qi Guo, Wei Xiong, Pan Su, Lingqun Ye, Yabo Li, Ling Zhong, Jianfei Qian, Yong Lu, Zhongming Zhao, Qing Yi","doi":"10.1038/s43018-025-00935-0","DOIUrl":"https://doi.org/10.1038/s43018-025-00935-0","url":null,"abstract":"Host effector CD4+ T cells emerge as critical mediators for tumor regression but whether they can be activated by adoptively transferred CD8+ T cells remains unknown. We previously reported that adoptive transfer of interleukin 9 (IL-9)-producing cytotoxic CD8+ T (Tc9) cells achieved long-term control of tumor growth. Here, we demonstrate that murine tumor-specific Tc9 cells control the outgrowth of antigen-loss relapsed tumors by recruiting and activating host effector CD4+ T cells. Tc9 cells secreted IL-24 and recruited CCR7-expressing conventional type 2 dendritic cells (cDC2 cells) into tumor-draining lymph nodes to prime host CD4+ T cells against relapsed tumors. Host CD4+ T cell or cDC2 deficiency impaired the ability of Tc9 cells to control relapsed tumor outgrowth. Additionally, intratumoral IL24 expression correlates with cDC2 and CD4+ T cell gene signatures in human cancers and their expression is associated with better patient survival. This study reports a mechanism for activation of tumor-specific CD4+ T cells in vivo.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780565","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

Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study. 格非他单抗治疗CAR-T细胞治疗失败后难治性或复发的弥漫性大B细胞淋巴瘤：一项2期LYSA研究

IF 23.5 1区医学

Nature cancer Pub Date : 2025-04-03 DOI: 10.1038/s43018-025-00941-2

Guillaume Cartron, Roch Houot, Yassine Al Tabaa, Fabien Le Bras, Loïc Ysebaert, Sylvain Choquet, Fabrice Jardin, Jacques-Olivier Bay, François-Xavier Gros, Franck Morschhauser, Olivier Casasnovas, Thomas Gastinne, Catherine Thieblemont, Magalie Joris, Laure Ricard, Caroline Regny, Laurianne Drieu La Rochelle, Pierre Feugier, Ambroise Marcais, Samuel Griolet, Karin Tarte, Camille Laurent, Pierre Sesques

{"title":"Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study.","authors":"Guillaume Cartron, Roch Houot, Yassine Al Tabaa, Fabien Le Bras, Loïc Ysebaert, Sylvain Choquet, Fabrice Jardin, Jacques-Olivier Bay, François-Xavier Gros, Franck Morschhauser, Olivier Casasnovas, Thomas Gastinne, Catherine Thieblemont, Magalie Joris, Laure Ricard, Caroline Regny, Laurianne Drieu La Rochelle, Pierre Feugier, Ambroise Marcais, Samuel Griolet, Karin Tarte, Camille Laurent, Pierre Sesques","doi":"10.1038/s43018-025-00941-2","DOIUrl":"https://doi.org/10.1038/s43018-025-00941-2","url":null,"abstract":"Persons with diffuse large B cell lymphoma (DLBCL) refractory or in first progression/relapsed (R/R) after chimeric antigen receptor T (CAR-T) cell therapy exhibit dramatic outcomes. We enrolled such persons in a phase 2 single-arm, nonblinded trial ( NCT04703686 ) to evaluate the efficacy and safety of glofitamab, a CD20-CD3 T cell-engaging bispecific antibody, using a short ramp-up regimen to reach full dose within 1 week. A total of 46 participants received at least one glofitamab infusion following obinutuzumab (anti-CD20 monoclonal antibody) pretreatment. The primary endpoint was overall survival (OS). Secondary endpoints included independent-assessed best overall metabolic response rate (OMRR) and complete metabolic response rate (CMRR), progression-free survival (PFS), duration of response, safety and tolerability and health-related quality of life. After a median follow-up of 15.3 months (95% confidence interval (CI), 10.1-17.7), the primary endpoint was met, achieving a median OS of 14.7 months (90% CI, 8.8-not reached). The best OMRR was 76.1%. The best CMRR was 45.7%. The median PFS was 3.8 months (95% CI, 2.4-19.6). Despite the shortened setup dosing, no excess cytokine release syndrome or neurotoxicity events were observed (grade ≥ 3, 0% for both). In conclusion, glofitamab improved OS in participants with R/R DLBCL after CAR-T cell therapy, with a favorable safety profile.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780632","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

Understanding the biology of lung cancer brain metastases. 了解肺癌脑转移的生物学。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-04-01 DOI: 10.1038/s43018-025-00974-7

Tiffanie Chouleur

引用次数: 0

Insight from the ESMO Targeted Anticancer Therapies Congress 2025. 2025年ESMO靶向抗癌疗法大会的见解。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-04-01 DOI: 10.1038/s43018-025-00953-y

Vincenzo Giacco

引用次数: 0

A multimodal integration model for non-invasive gallbladder lesions diagnosis. 非侵袭性胆囊病变诊断的多模态集成模型。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-04-01 DOI: 10.1038/s43018-025-00970-x

Eleni Skourti

引用次数: 0

Near-infrared optogenetic engineering of bacteria for cancer therapy. 用于癌症治疗的细菌近红外光基因工程。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-03-31 DOI: 10.1038/s43018-025-00931-4

引用次数: 0

Bispecific chimeric T cell receptors tackle tumor heterogeneity. 双特异性嵌合T细胞受体解决肿瘤异质性。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-03-31 DOI: 10.1038/s43018-025-00936-z

引用次数: 0

Systemic rewiring of dendritic cells by melanoma-secreted midkine impairs immune surveillance and response to immune checkpoint blockade. 黑素瘤分泌的中间因子对树突状细胞的系统性重新布线损害了免疫监视和对免疫检查点封锁的反应。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-03-28 DOI: 10.1038/s43018-025-00929-y

Xavier Catena, Marta Contreras-Alcalde, Naiara Juan-Larrea, Daniela Cerezo-Wallis, Tonantzin G Calvo, Cynthia Mucientes, David Olmeda, Javier Suárez, Sergio Oterino-Sogo, Lola Martínez, Diego Megías, David Sancho, Cristina Tejedo, Susana Frago, Diana Dudziak, Athanasios Seretis, Patrizia Stoitzner, María S Soengas

{"title":"Systemic rewiring of dendritic cells by melanoma-secreted midkine impairs immune surveillance and response to immune checkpoint blockade.","authors":"Xavier Catena, Marta Contreras-Alcalde, Naiara Juan-Larrea, Daniela Cerezo-Wallis, Tonantzin G Calvo, Cynthia Mucientes, David Olmeda, Javier Suárez, Sergio Oterino-Sogo, Lola Martínez, Diego Megías, David Sancho, Cristina Tejedo, Susana Frago, Diana Dudziak, Athanasios Seretis, Patrizia Stoitzner, María S Soengas","doi":"10.1038/s43018-025-00929-y","DOIUrl":"https://doi.org/10.1038/s43018-025-00929-y","url":null,"abstract":"Cutaneous melanomas express a high number of potential neoepitopes, yet a substantial fraction of melanomas shift into immunologically cold phenotypes. Using cellular systems, mouse models and large datasets, we identify the tumor-secreted growth factor midkine (MDK) as a multilayered inhibitor of antigen-presenting cells. Mechanistically, MDK acts systemically in primary tumors, lymph nodes and the bone marrow, promoting a STAT3-mediated impairment of differentiation, activation and function of dendritic cells (DCs), particularly, conventional type 1 DCs (cDC1s). Furthermore, MDK rewires DCs toward a tolerogenic state, impairing CD8+ T cell activation. Downregulating MDK improves DC-targeted vaccination, CD40 agonist treatment and immune checkpoint blockade in mouse models. Moreover, we present an MDK-associated signature in DCs that defines poor prognosis and immune checkpoint blockade resistance in individuals with cancer. An inverse correlation between MDK- and cDC1-associated signatures was observed in a variety of tumor types, broadening the therapeutic implications of MDK in immune-refractory malignancies.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742922","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