Pub Date : 2024-12-17DOI: 10.1038/s43018-024-00866-2
Shruthy Suresh Aggarwal, Cristina Andreani, Zihou Deng, Julia Frede, Polina Kameneva, Marta Kovatcheva, Goran Micevic, Fay Nicolson, Jens Puschhof, Morgan Roberts, Gang Wang, Dionysios C. Watson
Twelve early-career researchers who embarked on their independent research paths in 2024 reflect on their experience from their journey so far, describe the opportunities they received and the challenges they faced, and share their hopes and plans for the future.
{"title":"The 2024 generation","authors":"Shruthy Suresh Aggarwal, Cristina Andreani, Zihou Deng, Julia Frede, Polina Kameneva, Marta Kovatcheva, Goran Micevic, Fay Nicolson, Jens Puschhof, Morgan Roberts, Gang Wang, Dionysios C. Watson","doi":"10.1038/s43018-024-00866-2","DOIUrl":"10.1038/s43018-024-00866-2","url":null,"abstract":"Twelve early-career researchers who embarked on their independent research paths in 2024 reflect on their experience from their journey so far, describe the opportunities they received and the challenges they faced, and share their hopes and plans for the future.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"5 12","pages":"1774-1778"},"PeriodicalIF":23.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847099","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}
Pub Date : 2024-12-17DOI: 10.1038/s43018-024-00833-x
Lisa Hoffmann-Haas
{"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}
Pub Date : 2024-12-17DOI: 10.1038/s43018-024-00873-3
Elie Dolgin
T cell therapies for solid tumors took center stage, while new small-molecule drugs now offer targeted options for hard-to-treat cancers.
治疗实体瘤的T细胞疗法占据了中心位置，而现在新的小分子药物为难以治疗的癌症提供了有针对性的选择。
{"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}
Pub Date : 2024-12-16DOI: 10.1038/s43018-024-00871-5
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.
{"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}
Pub Date : 2024-12-16DOI: 10.1038/s43018-024-00870-6
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
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.
{"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}
Pub Date : 2024-12-13DOI: 10.1038/s43018-024-00854-6
Kailey N. Jackett, Alice T. Browne, Etan R. Aber, Miranda Clements, Rosandra N. Kaplan
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.
{"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}
Pub Date : 2024-12-11DOI: 10.1038/s43018-024-00869-z
Zhiao Shi, Jonathan T. Lei, John M. Elizarraras, Bing Zhang
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. Zhang and colleagues present FunMap, a computational framework that uses a pan-cancer functional map of over 10,000 protein-coding genes to identify functionally associated genes in large-scale datasets.
{"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":"10.1038/s43018-024-00869-z","url":null,"abstract":"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. Zhang and colleagues present FunMap, a computational framework that uses a pan-cancer functional map of over 10,000 protein-coding genes to identify functionally associated genes in large-scale datasets.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 1","pages":"205-222"},"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}
Pub Date : 2024-12-03DOI: 10.1038/s43018-024-00829-7
Janusz Rak
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.
{"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}
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