Nature cancer最新文献

{"title":"Overcoming immunoevasion in MHC class I-deficient cancers","authors":"Luca Danelli","doi":"10.1038/s43018-024-00852-8","DOIUrl":"10.1038/s43018-024-00852-8","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1788-1788"},"PeriodicalIF":23.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847095","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":"Cancer drug approvals and setbacks in 2024","authors":"Elie Dolgin","doi":"10.1038/s43018-024-00873-3","DOIUrl":"10.1038/s43018-024-00873-3","url":null,"abstract":"T cell therapies for solid tumors took center stage, while new small-molecule drugs now offer targeted options for hard-to-treat cancers.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1756-1758"},"PeriodicalIF":23.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847086","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":"Neoadjuvant immunotherapy marks a new era in oncology","authors":"Lisa Hoffmann-Haas","doi":"10.1038/s43018-024-00833-x","DOIUrl":"10.1038/s43018-024-00833-x","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1779-1779"},"PeriodicalIF":23.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847094","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":"Checkpoint blockade regulates T cell fate by supporting co-stimulation","authors":"","doi":"10.1038/s43018-024-00871-5","DOIUrl":"10.1038/s43018-024-00871-5","url":null,"abstract":"By tracking the fate of tumor-specific T cells mobilized in lymph nodes by dual blockade of PD-1 and TIGIT, we show that both exhausted T cells and effector T cells can emerge from a common progenitor. Signaling by the co-stimulatory receptors CD28 and CD226 is important for deciding between these two cell fates.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1796-1797"},"PeriodicalIF":23.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837823","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":"TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation","authors":"Katherine Nutsch, Karl L. Banta, Thomas D. Wu, Charles W. Tran, Stephanie Mittman, Ellen Duong, Barzin Y. Nabet, Yan Qu, Katherine Williams, Sören Müller, Namrata S. Patil, Eugene Y. Chiang, Ira Mellman","doi":"10.1038/s43018-024-00870-6","DOIUrl":"10.1038/s43018-024-00870-6","url":null,"abstract":"Blockade of immune checkpoints PD-1 and TIGIT has demonstrated activity in mouse tumor models and human patients with cancer. Although these coinhibitory receptors can restrict signaling in CD8+ T cells by regulating their associated co-stimulatory receptors CD28 and CD226, the functional consequences of combining PD-1 and TIGIT blockade remain poorly characterized. In mouse tumor models, we show that combination blockade elicited CD226-driven clonal expansion of tumor antigen-specific CD8+ T cells. The expanded clones emerged from a population of stem-like cells in draining lymph nodes, entering the blood as a previously unidentified single-phenotype, multiclonal population. Upon reaching the tumor, these transiting cells expanded further and differentiated into effector or exhausted T cells, with combination blockade restricting entry into the exhaustion pathway by favoring co-stimulation. Thus, PD-1 and TIGIT inhibition helps shape the repertoire of tumor-reactive CD8+ T cells in draining lymph nodes and determines their immunological fate in the tumor to enhance therapeutic benefit. Analysis of clinical trial samples suggests a similar mechanism may also occur in patients with cancer. Mellman and colleagues present a multiomic single-cell analysis of the effects of combined anti-TIGIT and anti-PD-1 blockade on T cell populations trafficking from the draining lymph node to the blood and tumor.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1834-1851"},"PeriodicalIF":23.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43018-024-00870-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837826","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":"How the bone microenvironment shapes the pre-metastatic niche and metastasis","authors":"Kailey N. Jackett, Alice T. Browne, Etan R. Aber, Miranda Clements, Rosandra N. Kaplan","doi":"10.1038/s43018-024-00854-6","DOIUrl":"10.1038/s43018-024-00854-6","url":null,"abstract":"The bone is a frequent metastatic site, with changes in the mineralized bone and the bone marrow milieu that can also prime other sites for metastasis by educating progenitor cells to support metastatic spread. Stromal and immune populations cooperatively maintain the organizationally complex bone niches and are dysregulated in the presence of a distant primary tumor and metastatic disease. Interrogating the bone niches that facilitate metastatic spread using innovative technologies holds the potential to aid in preventing metastasis in and mediated by the bone. Here, we review recent advances in bone niche biology and its adaptations in the context of cancer. Kaplan and colleagues discuss adaptations in the bone environment in the context of cancer, reflect on advanced technologies to study these bone niches and summarize how a remodeled bone marrow milieu can prime other sites for metastasis.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1800-1814"},"PeriodicalIF":23.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822318","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":"Mapping the functional network of human cancer through machine learning and pan-cancer proteogenomics.","authors":"Zhiao Shi, Jonathan T Lei, John M Elizarraras, Bing Zhang","doi":"10.1038/s43018-024-00869-z","DOIUrl":"https://doi.org/10.1038/s43018-024-00869-z","url":null,"abstract":"<p><p>Large-scale omics profiling has uncovered a vast array of somatic mutations and cancer-associated proteins, posing substantial challenges for their functional interpretation. Here we present a network-based approach centered on FunMap, a pan-cancer functional network constructed using supervised machine learning on extensive proteomics and RNA sequencing data from 1,194 individuals spanning 11 cancer types. Comprising 10,525 protein-coding genes, FunMap connects functionally associated genes with unprecedented precision, surpassing traditional protein-protein interaction maps. Network analysis identifies functional protein modules, reveals a hierarchical structure linked to cancer hallmarks and clinical phenotypes, provides deeper insights into established cancer drivers and predicts functions for understudied cancer-associated proteins. Additionally, applying graph-neural-network-based deep learning to FunMap uncovers drivers with low mutation frequency. This study establishes FunMap as a powerful and unbiased tool for interpreting somatic mutations and understudied proteins, with broad implications for advancing cancer biology and informing therapeutic strategies.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813826","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":"Anti-metastatic extracellular vesicles carrying DNA","authors":"Janusz Rak","doi":"10.1038/s43018-024-00829-7","DOIUrl":"10.1038/s43018-024-00829-7","url":null,"abstract":"Cancer cells often secrete extracellular vesicles (EVs), bubble-like structures thought to elicit pro-metastatic states. New work shows that colorectal cancers systemically export their genetic material attached to the surface of specific EVs. These DNA-carrying EVs are taken up by macrophages in the liver, activating anti-metastatic immune responses.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1793-1795"},"PeriodicalIF":23.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770548","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":"Unique structural configuration of EV-DNA primes Kupffer cell-mediated antitumor immunity to prevent metastatic progression","authors":"Inbal Wortzel,&nbsp;Yura Seo,&nbsp;Ife Akano,&nbsp;Lee Shaashua,&nbsp;Gabriel Cardial Tobias,&nbsp;Jakob Hebert,&nbsp;Kyung-A Kim,&nbsp;DooA Kim,&nbsp;Shani Dror,&nbsp;Yanshen Liu,&nbsp;Griffin Campbell Azrak,&nbsp;Michele Cioffi,&nbsp;Kofi Ennu Johnson,&nbsp;Tammy Hennika,&nbsp;Meshulam Zisha Twerski,&nbsp;Alexis Kushner,&nbsp;Robert Math,&nbsp;Yoon Dae Han,&nbsp;Dai Hoon Han,&nbsp;Minsun Jung,&nbsp;Juyeong Park,&nbsp;Soonmyung Paik,&nbsp;Jeon-Soo Shin,&nbsp;Min Goo Lee,&nbsp;Marco Vincenzo Russo,&nbsp;Daniel Zakheim,&nbsp;Jesse Barnes,&nbsp;Sunjoy Mehta,&nbsp;Katia Manova,&nbsp;Robert E. Schwartz,&nbsp;Basant Kumar Thakur,&nbsp;Nancy Boudreau,&nbsp;Irina Matei,&nbsp;Haiying Zhang,&nbsp;Simone Sidoli,&nbsp;Jacqueline Bromberg,&nbsp;Yael David,&nbsp;Han Sang Kim,&nbsp;David Lyden","doi":"10.1038/s43018-024-00862-6","DOIUrl":"10.1038/s43018-024-00862-6","url":null,"abstract":"Extracellular vesicles (EVs) transport biomolecules that mediate intercellular communication. We previously showed that EVs contain DNA (EV-DNA) representing the entire genome. However, the mechanism of genomic EV-DNA packaging and its role in cancer remain elusive. We now demonstrate that EV-DNA is predominantly localized on the vesicle surface and associated with uniquely modified and cleaved histones. Moreover, a genome-wide clustered regularly interspaced short palindromic repeats knockout screen revealed that immune developmental pathways and genes, including apoptotic peptidase activating factor 1 (APAF1) and neutrophil cytosolic factor 1 (NCF1), regulate EV-DNA packaging. Furthermore, in colorectal cancer models, uptake of EV-DNA by pre-metastatic liver Kupffer cells (KCs) activated DNA damage responses. This activation rewired KC cytokine production and promoted the formation of tertiary lymphoid structures, thereby suppressing liver metastasis. Conversely, loss of APAF1 decreased EV-DNA packaging and promoted liver metastasis. Importantly, colorectal cancer biopsy EV-DNA secretion could serve as a predictive biomarker for postoperative metastasis. Taken together, our findings indicate that uniquely chromatinized EV-DNA induces antitumor immunity. Lyden and colleagues find that immune developmental genes, such as apoptotic peptidase activating factor 1 (APAF1), support DNA packaging on the surface of tumor-derived extracellular vesicles that are taken up by resident liver macrophages, thereby suppressing metastasis.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1815-1833"},"PeriodicalIF":23.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770594","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 multiomic atlas identifies a treatment-resistant, bone marrow progenitor-like cell population in T cell acute lymphoblastic leukemia.","authors":"Jason Xu, Changya Chen, Jonathan H Sussman, Satoshi Yoshimura, Tiffaney Vincent, Petri Pölönen, Jianzhong Hu, Shovik Bandyopadhyay, Omar Elghawy, Wenbao Yu, Joseph Tumulty, Chia-Hui Chen, Elizabeth Y Li, Caroline Diorio, Rawan Shraim, Haley Newman, Lahari Uppuluri, Alexander Li, Gregory M Chen, David W Wu, Yang-Yang Ding, Jessica A Xu, Damjan Karanfilovski, Tristan Lim, Miles Hsu, Anusha Thadi, Kyung Jin Ahn, Chi-Yun Wu, Jacqueline Peng, Yusha Sun, Alice Wang, Rushabh Mehta, David Frank, Lauren Meyer, Mignon L Loh, Elizabeth A Raetz, Zhiguo Chen, Brent L Wood, Meenakshi Devidas, Kimberly P Dunsmore, Stuart S Winter, Ti-Cheng Chang, Gang Wu, Stanley B Pounds, Nancy R Zhang, William Carroll, Stephen P Hunger, Kathrin Bernt, Jun J Yang, Charles G Mullighan, Kai Tan, David T Teachey","doi":"10.1038/s43018-024-00863-5","DOIUrl":"10.1038/s43018-024-00863-5","url":null,"abstract":"<p><p>Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, the cellular and genetic factors contributing to resistance and relapse remain unknown. Here we linked tumor subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic analysis to a diverse cohort of 40 T-ALL cases. We identified a bone marrow progenitor (BMP)-like leukemia subpopulation associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL and revealed that NOTCH1 mutations additively drive T-ALL blasts away from the BMP-like state. Through in silico and in vitro drug screenings, we identified a therapeutic vulnerability of BMP-like blasts to apoptosis-inducing agents including venetoclax. Collectively, our study establishes multiomic signatures for rapid risk stratification and targeted treatment of high-risk T-ALL.</p>","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":" ","pages":""},"PeriodicalIF":23.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716449","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}