Nature cancer最新文献

{"title":"Bispecific chimeric T cell receptors tackle tumor heterogeneity.","authors":"","doi":"10.1038/s43018-025-00936-z","DOIUrl":"10.1038/s43018-025-00936-z","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"571-572"},"PeriodicalIF":23.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753541","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":"Targeting both death and paracaspase domains of MALT1 with antisense oligonucleotides overcomes resistance to immune-checkpoint inhibitors.","authors":"Yuwei Tao, Chen Tian, Shaolong Qi, Ziqi Jia, Zheng Xu, Jingjing Meng, Guoyuan Xu, Haitian Hu, Xuxiang Wang, Tengjiang Zhang, Huiwen You, Xun Lan, Xin Lin, Guocan Yu, Haitao Zhou, Jiaqi Liu, Hanqiu Zheng","doi":"10.1038/s43018-025-00930-5","DOIUrl":"10.1038/s43018-025-00930-5","url":null,"abstract":"<p><p>Targeting MALT1's paracaspase activity has been explored for B cell lymphoma and solid tumors. While the role of MALT1 in promoting cancer cell proliferation has been investigated, its involvement in immune evasion is unclear. Here we report that MALT1 promotes immune evasion through its paracaspase and death domain. In a paracaspase-dependent manner, MALT1 protects CD274 mRNA from degradation by its cleavage of ROQUIN1 and ROQUIN2. In a death-domain-dependent manner, MALT1 promotes the proliferation and polarization of tumor-associated macrophages to generate an immunosuppressive tumor microenvironment. Targeting MALT1 with antisense oligonucleotides inhibits PD-L1 expression in patient-derived tumor cells and suppresses the proliferation and M2-like polarization of tumor-associated macrophages isolated from patients with cancer. In preclinical models of solid tumors in female mice, treatment with MALT1 antisense oligonucleotides overcomes resistance to immune-checkpoint inhibitors. Together, our study demonstrates that targeting MALT1 is a potential strategy to overcome immune-checkpoint inhibitor resistance.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"702-717"},"PeriodicalIF":23.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616285","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":"Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy.","authors":"Sylvain Simon, Grace Bugos, Rachel Prins, Anusha Rajan, Arulmozhi Palani, Kersten Heyer, Andrew Stevens, Longhui Zeng, Kirsten A Thompson, Pinar A Atilla, Jason P Price, Mitchell G Kluesner, Carla A Jaeger-Ruckstuhl, Tamer B Shabaneh, James M Olson, Xiaolei Su, Stanley R Riddell","doi":"10.1038/s43018-025-00927-0","DOIUrl":"10.1038/s43018-025-00927-0","url":null,"abstract":"<p><p>The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is effective in B cell malignancies. However, the persistence of cancer cells with low levels or complete absence of the target antigen, thereby evading detection by CAR T cells, leads to relapse. These evasion mechanisms highlight the need for receptors with enhanced sensitivity and multispecificity. We introduce a synthetic chimeric T cell receptor (ChTCR) that confers superior antigen sensitivity compared with CARS and previous hybrid TCR designs and is readily adapted for bispecific targeting. ChTCRs replicate the structure of natural TCRs, form classical immune synapses and demonstrate TCR-like signaling. T cells expressing bispecific ChTCRs (Bi-ChTCRs) are more effective than bispecific CAR T cells in eradicating tumors with heterogeneous antigen expression in vivo in female mice. The Bi-ChTCR architecture is resilient and can be designed to target pairs of B cell and multiple myeloma antigens. These findings provide a widely applicable strategy to combat tumor heterogeneity and prevent relapse.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"647-665"},"PeriodicalIF":23.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649729","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":"Targeting anti-androgen therapy resistance through epigenetic rewiring.","authors":"Kate E Dunmore, David S Rickman","doi":"10.1038/s43018-025-00906-5","DOIUrl":"10.1038/s43018-025-00906-5","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"564-566"},"PeriodicalIF":23.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657807","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":"Exploiting HLA-DR mismatches for CAR therapy in acute myeloid leukemia.","authors":"May Daher, Katayoun Rezvani","doi":"10.1038/s43018-025-00913-6","DOIUrl":"10.1038/s43018-025-00913-6","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"561-563"},"PeriodicalIF":23.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701104","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":"A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.","authors":"Jinming Wang, Penghui Xu, Zhongzhong Ji, Chaping Cheng, Yiyun Liu, Genyu Du, Shilei Zhang, Juju Miao, Deng Wang, Ruoyang Chen, Dawei Li, Kai Zhang, Huifang Zhao, Yujiao Sun, Xinyu Chen, Na Jing, Kaiyuan Liu, Yuman He, Xialian Xi, Yingchao Zhang, Nan Wang, Longmei Xu, Jufang Yao, Xiaomei Gao, Jianhua Zhou, Songqing Fan, Xiaorui Wang, Shuxian Dong, Fangli Chen, Jian Hou, Ming Zhang, Wei-Qiang Gao, Lijing Shen, Pengcheng Zhang, Helen He Zhu","doi":"10.1038/s43018-025-00933-2","DOIUrl":"10.1038/s43018-025-00933-2","url":null,"abstract":"<p><p>The spleen plays a critical role in the pathogenesis of leukemia. However, our understanding of the splenic niche is very limited. Herein, we report that induced expression of the secreted protein Gremlin 1 in a mouse model restrains chronic myeloid leukemia (CML) progression and synergizes with tyrosine kinase inhibitor treatment, whereas blockade of Gremlin 1 promotes CML development. Intriguingly, the effect of Gremlin 1 is most evident in the spleen but not in the bone marrow. Gremlin 1 induces apoptosis of leukemic stem cells via antagonizing the BMP pathway. Single-cell RNA sequencing and experimental validation together show that Gremlin 1 marks a unique stromal cell population in the spleens of both mice and humans. Genetic ablation of Gremlin 1⁺ cells leads to accelerated CML progression. Collectively, Gremlin 1 and Gremlin 1⁺ cells are key defensive niche components in the spleen that limit CML progression, revealing an unprecedented mechanism for the body to fight off leukemia.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":"666-681"},"PeriodicalIF":23.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649639","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":"Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial","authors":"Won Seog Kim,&nbsp;Tae Min Kim,&nbsp;Seok-Goo Cho,&nbsp;Isidro Jarque,&nbsp;Elżbieta Iskierka-Jażdżewska,&nbsp;Li Mei Poon,&nbsp;H. Miles Prince,&nbsp;Huilai Zhang,&nbsp;Junning Cao,&nbsp;Mingzhi Zhang,&nbsp;Benoît Tessoulin,&nbsp;Sung Yong Oh,&nbsp;Francesca Lim,&nbsp;Cecilia Carpio,&nbsp;Tran-Der Tan,&nbsp;Sabarish Ayyappan,&nbsp;Antonio Gutierrez,&nbsp;Jingxian Cai,&nbsp;Melanie Ufkin,&nbsp;Saleem Shariff,&nbsp;Jurriaan Brouwer-Visser,&nbsp;Aafia Chaudhry,&nbsp;Hesham Mohamed,&nbsp;Srikanth Ambati,&nbsp;Jan Walewski,&nbsp;on behalf of the ELM-2 Investigators","doi":"10.1038/s43018-025-00921-6","DOIUrl":"10.1038/s43018-025-00921-6","url":null,"abstract":"The phase 2, multicohort, ongoing ELM-2 study evaluates odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma after ≥2 lines of therapy. Here primary analysis of the diffuse large B cell lymphoma (DLBCL) cohort is reported. Patients received intravenous odronextamab in 21-day cycles until progression or unacceptable toxicity, with cycle 1 step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary endpoint was objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS) and overall survival. A total of 127 patients were enrolled. At the 29.9-month efficacy follow-up, the ORR was 52.0% and CR rate was 31.5%. Median durations of response and CR were 10.2 and 17.9 months, respectively. Undetectable minimal residual disease at cycle 4 day 15 was associated with PFS benefit. With a step-up of 0.7 to 4 to 20 mg (n = 60), CRS was the most common treatment-emergent adverse event (53.3% (grade ≥3, 1.7%)). No immune effector cell-associated neurotoxicity syndrome was reported. Infections were reported in 82/127 (64.6%) patients (grade ≥3, 38.6%; coronavirus disease 2019, 18.1% (grade ≥3, 12.6%)). In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care. Clinical trial registration: NCT03888105 . Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 3","pages":"528-539"},"PeriodicalIF":23.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649658","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":"Glioblastoma’s widespread integration into neuronal networks","authors":"Julieta Alfonso","doi":"10.1038/s43018-025-00939-w","DOIUrl":"10.1038/s43018-025-00939-w","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 3","pages":"408-408"},"PeriodicalIF":23.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43018-025-00939-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616282","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":"Long-term results with nivolumab and ipilimumab in melanoma","authors":"Vincenzo Giacco","doi":"10.1038/s43018-025-00938-x","DOIUrl":"10.1038/s43018-025-00938-x","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 3","pages":"407-407"},"PeriodicalIF":23.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43018-025-00938-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616283","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":"Neutrophils take their PICk to promote breast cancer","authors":"Claudia Tulotta,&nbsp;Oliver Soehnlein","doi":"10.1038/s43018-025-00925-2","DOIUrl":"10.1038/s43018-025-00925-2","url":null,"abstract":"Tumor-infiltrating neutrophils can have either pro-tumoral potential or anti-tumoral potential. Physical contact between heterogeneous neutrophils and tumor cells in the tumor microenvironment is now shown to facilitate the malignant progression of breast cancer.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 3","pages":"409-411"},"PeriodicalIF":23.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616284","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}