Nature cancer最新文献_第3页

p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2⁺ breast cancer that limits trastuzumab deruxtecan efficacy. p95HER2是HER2癌蛋白的一种截断形式，在HER2阳性乳腺癌中驱动免疫抑制程序，限制曲妥珠单抗德鲁西替康的疗效。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-27 DOI: 10.1038/s43018-025-00969-4

Dong Hu, Xiaoshuang Lyu, Zheqi Li, Prasanna Ekambaram, Anushka Dongre, Tanner Freeman, Marion Joy, Jennifer M Atkinson, Daniel D Brown, Zongyou Cai, Neil M Carleton, Hannah E Crentsil, John Little, Felicia Kemp, Linda R Klei, Maria Beecher, Jeff Sperinde, Weidong Huang, Heikki Joensuu, Ashok Srinivasan, Katherine L Pogue-Geile, Ying Wang, Huichen Feng, Lisa D Eli, Alshad S Lalani, Jian Zou, George C Tseng, Tullia C Bruno, Adrian V Lee, Steffi Oesterreich, Norman Wolmark, Carmen J Allegra, Samuel A Jacobs, Linda M McAllister-Lucas, Peter C Lucas

{"title":"p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2+ breast cancer that limits trastuzumab deruxtecan efficacy.","authors":"Dong Hu, Xiaoshuang Lyu, Zheqi Li, Prasanna Ekambaram, Anushka Dongre, Tanner Freeman, Marion Joy, Jennifer M Atkinson, Daniel D Brown, Zongyou Cai, Neil M Carleton, Hannah E Crentsil, John Little, Felicia Kemp, Linda R Klei, Maria Beecher, Jeff Sperinde, Weidong Huang, Heikki Joensuu, Ashok Srinivasan, Katherine L Pogue-Geile, Ying Wang, Huichen Feng, Lisa D Eli, Alshad S Lalani, Jian Zou, George C Tseng, Tullia C Bruno, Adrian V Lee, Steffi Oesterreich, Norman Wolmark, Carmen J Allegra, Samuel A Jacobs, Linda M McAllister-Lucas, Peter C Lucas","doi":"10.1038/s43018-025-00969-4","DOIUrl":"https://doi.org/10.1038/s43018-025-00969-4","url":null,"abstract":"Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies and immuno-oncology agents poses a major challenge in treating HER2-positive breast cancer. Here we demonstrate that p95HER2, a truncated form of HER2, drives immune evasion in HER2-positive female breast cancer, enhancing tumor growth and conferring therapy resistance. This stems from the unique ability of p95HER2 to promote cancer cell-intrinsic programmed death ligand 1 expression and secretion of immunosuppressive mediators including interleukin 6. In preclinical models, this impairs the efficacy of trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate (ADC) that relies on immunogenic responses to cell death for full efficacy. Importantly, we find that neratinib potently directs proteasomal degradation of p95HER2, relieving its immunosuppressive effects, and provide proof of concept that neratinib and/or agents targeting p95HER2 downstream mediators can restore antitumor immunity and trastuzumab deruxtecan efficacy. This study reveals a p95HER2-specific therapy resistance mechanism in HER2-positive female breast cancer and highlights the potential value of targeting p95HER2 to improve outcomes with ADCs or immuno-oncology agents.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512215","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

Concurrent inhibition of tumor growth and metastasis by a lipidated nanophotosensitizer tracing and disabling tumor extracellular vesicles. 脂化纳米光敏剂追踪和禁用肿瘤细胞外囊泡对肿瘤生长和转移的同时抑制。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-24 DOI: 10.1038/s43018-025-00997-0

Guifeng Miao, Zhanhao Shang, Xinyue Wang, Jibin Zhang, Mingheng Xu, Peiyi He, Qinjie Zhong, Xiaoxi Zhao, Guozhu Tan, Xiaorui Wang

{"title":"Concurrent inhibition of tumor growth and metastasis by a lipidated nanophotosensitizer tracing and disabling tumor extracellular vesicles.","authors":"Guifeng Miao, Zhanhao Shang, Xinyue Wang, Jibin Zhang, Mingheng Xu, Peiyi He, Qinjie Zhong, Xiaoxi Zhao, Guozhu Tan, Xiaorui Wang","doi":"10.1038/s43018-025-00997-0","DOIUrl":"https://doi.org/10.1038/s43018-025-00997-0","url":null,"abstract":"Cancer cells promote tumor growth and metastasis through tumor extracellular vesicle (TEV)-mediated intercellular and intertissue communication. Inhibiting TEVs represents a promising strategy to suppress metastasis; however, effectively and selectively disabling TEVs remains challenging. Herein, we developed palmitic acid surface-displayed nanoparticles using an adjacent hydrophilic molecular engineering strategy. Unexpectedly, these lipidated nanoparticles were not only efficiently taken up and distributed within tumor cells but also coupled with TEV generation, enabling active tracing of TEVs. Exploiting their dual tumor spatial distribution (intracellular and intra-TEV), a lipidated nanophotosensitizer was constructed for metastasis therapy. Under near-infrared light irradiation at the primary tumor site, both intracellular and intra-TEV reactive oxygen species were generated synchronously. This led to photodynamic suppression of the primary tumor and blocked intercellular and intertissue communication by disabling TEVs, effectively inhibiting tumor growth and metastasis in multiple tumor models in female mice. Overall, this work reports a therapeutic paradigm for concurrently inhibiting tumor growth and metastasis.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485152","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

Innate immunity and the NF-κB pathway control prostate stem cell plasticity, reprogramming and tumor initiation. 先天免疫和NF-κB通路控制前列腺干细胞的可塑性、重编程和肿瘤发生。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-23 DOI: 10.1038/s43018-025-00994-3

Chen Jiang, Yura Song, Sandrine Rorive, Justine Allard, Elisavet Tika, Zahra Zahedi, Christine Dubois, Isabelle Salmon, Alejandro Sifrim, Cédric Blanpain

{"title":"Innate immunity and the NF-κB pathway control prostate stem cell plasticity, reprogramming and tumor initiation.","authors":"Chen Jiang, Yura Song, Sandrine Rorive, Justine Allard, Elisavet Tika, Zahra Zahedi, Christine Dubois, Isabelle Salmon, Alejandro Sifrim, Cédric Blanpain","doi":"10.1038/s43018-025-00994-3","DOIUrl":"10.1038/s43018-025-00994-3","url":null,"abstract":"Prostate epithelium develops from multipotent stem cells, which are replaced in adult life by different lineage-restricted basal and luminal unipotent stem cells. Deletion of Pten re-induces multipotency in basal cells (BCs); however, the molecular mechanisms regulating BC plasticity and tumor initiation are poorly understood. Here we showed that Pten deletion in BCs led to distinct cell fate reprogramming and tumor initiation in a regionalized manner. Single-cell RNA sequencing, ATAC-seq and in situ characterization revealed that following Pten deletion in anterior and dorsolateral prostates, BCs were highly plastic and reprogrammed into a hillock-like state, progressing into a proximal-like luminal state before giving rise to invasive tumors. This BC reprogramming was associated with the activation of innate immunity. Pharmacological targeting of interleukin-1, JAK-STAT and NF-κB as well as genetic deletion of Nfkb inhibit Pten-induced cell plasticity and reprogramming in a cellular autonomous manner, opening new opportunities for prevention and treatment of prostate cancer.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476089","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

Doxorubicin cardiotoxicity is mediated by neutrophil extracellular traps. 阿霉素心脏毒性是由中性粒细胞胞外陷阱介导的。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-20 DOI: 10.1038/s43018-025-00989-0

引用次数: 0

Targeting the tRNA m¹A modifier TRMT6 for colorectal cancer therapy. 靶向tRNA m1A修饰子TRMT6用于结直肠癌治疗。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-20 DOI: 10.1038/s43018-025-00978-3

引用次数: 0

A peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma: a phase 1 trial. 一种针对CMV抗原pp65的肽疫苗用于复发性高级别胶质瘤和髓母细胞瘤的儿童和年轻人：一项1期试验

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-12 DOI: 10.1038/s43018-025-00998-z

Eric M Thompson, David M Ashley, Katayoun Ayasoufi, Pamela Norberg, Gerald Archer, Evan D Buckley, James E Herndon, Ashley Walter, Bridget Archambault, Charlene Flahiff, Denise Jaggers, Laura Gorski, Luis A Sanchez, Kendra Congdon, Kelly Hotchkiss, Sarah L Cook, Eliese Moelker, Gordana Vlahovic, Elizabeth Reap, Kristin Schroeder, Dina Randazzo, Annick Desjardins, Margaret O Johnson, Katherine Peters, Mustafa Khasraw, Henry Friedman, Duane A Mitchell, John H Sampson, Daniel Landi

{"title":"A peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma: a phase 1 trial.","authors":"Eric M Thompson, David M Ashley, Katayoun Ayasoufi, Pamela Norberg, Gerald Archer, Evan D Buckley, James E Herndon, Ashley Walter, Bridget Archambault, Charlene Flahiff, Denise Jaggers, Laura Gorski, Luis A Sanchez, Kendra Congdon, Kelly Hotchkiss, Sarah L Cook, Eliese Moelker, Gordana Vlahovic, Elizabeth Reap, Kristin Schroeder, Dina Randazzo, Annick Desjardins, Margaret O Johnson, Katherine Peters, Mustafa Khasraw, Henry Friedman, Duane A Mitchell, John H Sampson, Daniel Landi","doi":"10.1038/s43018-025-00998-z","DOIUrl":"https://doi.org/10.1038/s43018-025-00998-z","url":null,"abstract":"The human cytomegalovirus (CMV) antigen pp65 is expressed in high-grade glioma (HGG) and medulloblastoma but not in the adjacent brain. This single-arm phase 1 trial ( NCT03299309 ) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targeting pp65 in individuals (3-35 years old) with recurrent HGG or medulloblastoma. Thirty-six individuals with HGG received PEP-CMV. The mean age was 22.75 ± 9.34 years. The primary outcome, percentage of unacceptable toxicity, was met. The maximum-grade adverse events (AE) related to PEP-CMV were 17 grade 1 AEs, 15 grade 2 AEs, 1 grade 3 AE (pyramidal tract syndrome) and 1 grade 4 AE (cerebral edema). As a secondary outcome, in 21 individuals with evaluable data, T cell reactivity, measured as change in baseline interferon-γ pp65 enzyme-linked immunospot assay reactivity, had an estimated increase of 46 spots (95% confidence interval (95% CI): 8, 194) after treatment with PEP-CMV. As exploratory endpoints, the median progression-free survival was 2.5 months (95% CI: 2.2, 3.2), and median overall survival was 6.5 months (95% CI: 4.6, 8.4). PEP-CMV is well tolerated and elicits an antigen-specific immune response in individuals with multiply recurrent HGG. Only two individuals with medulloblastoma were enrolled, showing one grade 3 encephalopathy possibly related to PEP-CMV, while neither had postvaccine immune assessments due to progression-free survival and overall survival less than 2 months.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285446","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

Aging alters the response to CAR T cell therapy. 衰老会改变对CAR - T细胞疗法的反应。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-12 DOI: 10.1038/s43018-025-00983-6

引用次数: 0

Long-acting IL-2 release from pressure-fused biomineral tablets promotes antitumor immune response. 加压生物矿物质片释放长效IL-2促进抗肿瘤免疫反应。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-10 DOI: 10.1038/s43018-025-00993-4

Jinpeng Han, Shenqiang Wang, Weifeng Fang, Yinxian Yang, Ruyi Zhou, Yuqi Zhang, Jicheng Yu, Ruikang Tang, Zhaoming Liu, Zhen Gu

{"title":"Long-acting IL-2 release from pressure-fused biomineral tablets promotes antitumor immune response.","authors":"Jinpeng Han, Shenqiang Wang, Weifeng Fang, Yinxian Yang, Ruyi Zhou, Yuqi Zhang, Jicheng Yu, Ruikang Tang, Zhaoming Liu, Zhen Gu","doi":"10.1038/s43018-025-00993-4","DOIUrl":"https://doi.org/10.1038/s43018-025-00993-4","url":null,"abstract":"Long-acting controlled drug release formulations are highly desired for potentiating efficacy and reducing administration frequency. Here we present a kinetically controllable long-term interleukin-2 (IL-2) release platform by the fusion and boundary elimination of calcium carbonate and calcium phosphate amorphous phases. Unlike mixtures, a group of hybrid biominerals with the chemical formula Ca(CO3)x(PO4)2(1-x)/3 (CaCPs, 0 < x < 1) was fabricated under high pressure (2 GPa), and the CaCPs showed crystallization-driven release behaviors to optimize the in vivo fate of IL-2. Ca(CO3)1/2(PO4)1/3 dynamically remodeled immunosuppressive tumor microenvironments, preferentially activated cytotoxic and memory T cells by improving IL-2 redistribution and achieved weeks-long IL-2 retention in tumors with high tolerance and biosafety. In a melanoma model in female mice, Ca(CO3)1/2(PO4)1/3 revealed superior antitumor effects to inhibit local tumor recurrence, hinder the growth of distant untreated tumors and maintain long-term T cell responses against the rechallenged metastatic tumors.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266661","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

Biomineral tablets for long-acting IL-2 immunotherapy. 生物矿物质片用于长效IL-2免疫治疗。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-10 DOI: 10.1038/s43018-025-00951-0

Jianping Liu, Xiaoyuan Chen

引用次数: 0

crossNN is an explainable framework for cross-platform DNA methylation-based classification of tumors. crossNN是跨平台的基于DNA甲基化的肿瘤分类的可解释框架。

IF 23.5 1区医学

Nature cancer Pub Date : 2025-06-06 DOI: 10.1038/s43018-025-00976-5

Dongsheng Yuan, Robin Jugas, Petra Pokorna, Jaroslav Sterba, Ondrej Slaby, Simone Schmid, Christin Siewert, Brendan Osberg, David Capper, Skarphedinn Halldorsson, Einar O Vik-Mo, Pia S Zeiner, Katharina J Weber, Patrick N Harter, Christian Thomas, Anne Albers, Markus Rechsteiner, Regina Reimann, Anton Appelt, Ulrich Schüller, Nabil Jabareen, Sebastian Mackowiak, Naveed Ishaque, Roland Eils, Sören Lukassen, Philipp Euskirchen

{"title":"crossNN is an explainable framework for cross-platform DNA methylation-based classification of tumors.","authors":"Dongsheng Yuan, Robin Jugas, Petra Pokorna, Jaroslav Sterba, Ondrej Slaby, Simone Schmid, Christin Siewert, Brendan Osberg, David Capper, Skarphedinn Halldorsson, Einar O Vik-Mo, Pia S Zeiner, Katharina J Weber, Patrick N Harter, Christian Thomas, Anne Albers, Markus Rechsteiner, Regina Reimann, Anton Appelt, Ulrich Schüller, Nabil Jabareen, Sebastian Mackowiak, Naveed Ishaque, Roland Eils, Sören Lukassen, Philipp Euskirchen","doi":"10.1038/s43018-025-00976-5","DOIUrl":"https://doi.org/10.1038/s43018-025-00976-5","url":null,"abstract":"DNA methylation-based classification of (brain) tumors has emerged as a powerful and indispensable diagnostic technique. Initial implementations used methylation microarrays for data generation, while most current classifiers rely on a fixed methylation feature space. This makes them incompatible with other platforms, especially different flavors of DNA sequencing. Here, we describe crossNN, a neural network-based machine learning framework that can accurately classify tumors using sparse methylomes obtained on different platforms and with different epigenome coverage and sequencing depth. It outperforms other deep and conventional machine learning models regarding accuracy and computational requirements while still being explainable. We use crossNN to train a pan-cancer classifier that can discriminate more than 170 tumor types across all organ sites. Validation in more than 5,000 tumors profiled on different platforms, including nanopore and targeted bisulfite sequencing, demonstrates its robustness and scalability with 99.1% and 97.8% precision for the brain tumor and pan-cancer models, respectively.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248857","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