Nature Reviews Cancer最新文献_第10页

Convergent inducers and effectors of T cell paralysis in the tumour microenvironment 肿瘤微环境中T细胞瘫痪的趋同诱导因子和效应因子

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-24 DOI: 10.1038/s41568-024-00761-z

Douglas Hanahan, Olivier Michielin, Mikael J. Pittet

{"title":"Convergent inducers and effectors of T cell paralysis in the tumour microenvironment","authors":"Douglas Hanahan, Olivier Michielin, Mikael J. Pittet","doi":"10.1038/s41568-024-00761-z","DOIUrl":"10.1038/s41568-024-00761-z","url":null,"abstract":"Tumorigenesis embodies the formation of a heterotypic tumour microenvironment (TME) that, among its many functions, enables the evasion of T cell-mediated immune responses. Remarkably, most TME cell types, including cancer cells, fibroblasts, myeloid cells, vascular endothelial cells and pericytes, can be stimulated to deploy immunoregulatory programmes. These programmes involve regulatory inducers (signals-in) and functional effectors (signals-out) that impair CD8+ and CD4+ T cell activity through cytokines, growth factors, immune checkpoints and metabolites. Some signals target specific cell types, whereas others, such as transforming growth factor-β (TGFβ) and prostaglandin E2 (PGE2), exert broad, pleiotropic effects; as signals-in, they trigger immunosuppressive programmes in most TME cell types, and as signals-out, they directly inhibit T cells and also modulate other cells to reinforce immunosuppression. This functional diversity and redundancy pose a challenge for therapeutic targeting of the immune-evasive TME. Fundamentally, the commonality of regulatory programmes aimed at abrogating T cell activity, along with paracrine signalling between cells of the TME, suggests that many normal cell types are hard-wired with latent functions that can be triggered to prevent inappropriate immune attack. This intrinsic capability is evidently co-opted throughout the TME, enabling tumours to evade immune destruction. In this Review, Hanahan et al. discuss how, in response to tumorigenesis, nearly all cell types in the tumour microenvironment can be programmed to mediate — as functionally distinct subtypes — immunosuppressive programmes that result in the inhibition of antitumour T cell activity and the evasion of immune destruction.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 1","pages":"41-58"},"PeriodicalIF":72.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488367","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

High-resolution measurement of individual telomere lengths with Telo-seq 利用 Telo-seq 高分辨率测量单个端粒长度

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-22 DOI: 10.1038/s41568-024-00767-7

Carly Tyer

引用次数: 0

Emerging strategies to investigate the biology of early cancer 研究早期癌症生物学的新策略

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-21 DOI: 10.1038/s41568-024-00754-y

Ran Zhou, Xiwen Tang, Yuan Wang

{"title":"Emerging strategies to investigate the biology of early cancer","authors":"Ran Zhou, Xiwen Tang, Yuan Wang","doi":"10.1038/s41568-024-00754-y","DOIUrl":"10.1038/s41568-024-00754-y","url":null,"abstract":"Early detection and intervention of cancer or precancerous lesions hold great promise to improve patient survival. However, the processes of cancer initiation and the normal–precancer–cancer progression within a non-cancerous tissue context remain poorly understood. This is, in part, due to the scarcity of early-stage clinical samples or suitable models to study early cancer. In this Review, we introduce clinical samples and model systems, such as autochthonous mice and organoid-derived or stem cell-derived models that allow longitudinal analysis of early cancer development. We also present the emerging techniques and computational tools that enhance our understanding of cancer initiation and early progression, including direct imaging, lineage tracing, single-cell and spatial multi-omics, and artificial intelligence models. Together, these models and techniques facilitate a more comprehensive understanding of the poorly characterized early malignant transformation cascade, holding great potential to unveil key drivers and early biomarkers for cancer development. Finally, we discuss how these new insights can potentially be translated into mechanism-based strategies for early cancer detection and prevention. Understanding the early steps of cancer development is crucial for cancer prevention. In this Review, the authors summarize the advantages and limitations of clinical samples, autochthonous mouse models and organoid models, alongside advanced techniques such as direct imaging, lineage tracing and AI, to enhance understanding of early cancer progression.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"850-866"},"PeriodicalIF":72.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452535","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

New horizons in our understanding of precursor multiple myeloma and early interception 我们对多发性骨髓瘤前兆和早期阻断的认识新视野

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-16 DOI: 10.1038/s41568-024-00755-x

David M. Cordas dos Santos, Rosa Toenges, Luca Bertamini, Jean-Baptiste Alberge, Irene M. Ghobrial

{"title":"New horizons in our understanding of precursor multiple myeloma and early interception","authors":"David M. Cordas dos Santos, Rosa Toenges, Luca Bertamini, Jean-Baptiste Alberge, Irene M. Ghobrial","doi":"10.1038/s41568-024-00755-x","DOIUrl":"10.1038/s41568-024-00755-x","url":null,"abstract":"Multiple myeloma is an incurable plasma cell malignancy that evolves over decades through the selection and malignant transformation of monoclonal plasma cells. The evolution from precursor states to symptomatic disease is characterized by an increasing complexity of genomic alterations within the plasma cells and a remodelling of the microenvironment towards an immunosuppressive state. Notably, in patients with advanced disease, similar mechanisms of tumour escape and immune dysfunction mediate resistance to modern T cell-based therapies, such as T cell-engaging bispecific antibodies and chimeric antigen receptor (CAR)-T cells. Thus, an increasing number of clinical trials are assessing the efficiency and safety of these therapies in individuals with newly diagnosed multiple myeloma and high-risk smoldering multiple myeloma. In this Review, we summarize the current knowledge about tumour intrinsic and extrinsic processes underlying progression from precursor states to symptomatic myeloma and discuss the rationale for early interception including the use of T cell-redirecting therapies. Multiple myeloma is a plasma cell malignancy that is currently incurable. Cordas dos Santos et al. describe how multiple myeloma arises from precursor states and how T cell-redirecting therapies might be used to intercept disease progression at these earlier stages to improve patient outcomes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"867-886"},"PeriodicalIF":72.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439736","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

Epigenomic heterogeneity as a source of tumour evolution 表观基因组异质性是肿瘤演变的源头

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-16 DOI: 10.1038/s41568-024-00757-9

Marthe Laisné, Mathieu Lupien, Céline Vallot

{"title":"Epigenomic heterogeneity as a source of tumour evolution","authors":"Marthe Laisné, Mathieu Lupien, Céline Vallot","doi":"10.1038/s41568-024-00757-9","DOIUrl":"10.1038/s41568-024-00757-9","url":null,"abstract":"In the past decade, remarkable progress in cancer medicine has been achieved by the development of treatments that target DNA sequence variants. However, a purely genetic approach to treatment selection is hampered by the fact that diverse cell states can emerge from the same genotype. In multicellular organisms, cell-state heterogeneity is driven by epigenetic processes that regulate DNA-based functions such as transcription; disruption of these processes is a hallmark of cancer that enables the emergence of defective cell states. Advances in single-cell technologies have unlocked our ability to quantify the epigenomic heterogeneity of tumours and understand its mechanisms, thereby transforming our appreciation of how epigenomic changes drive cancer evolution. This Review explores the idea that epigenomic heterogeneity and plasticity act as a reservoir of cell states and therefore as a source of tumour evolution. Best practices to quantify epigenomic heterogeneity and explore its various causes and consequences are discussed, including epigenomic reprogramming, stochastic changes and lasting memory. The design of new therapeutic approaches to restrict epigenomic heterogeneity, with the long-term objective of limiting cancer development and progression, is also addressed. Single-cell epigenomic technologies are refining our understanding of cancer evolution. Here Laisné et al. describe how epigenomic heterogeneity generates dynamic reservoirs of tumour cell states, through epigenomic reprogramming and selection among stochastic changes, which can be leveraged in the design of novel therapies.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 1","pages":"7-26"},"PeriodicalIF":72.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440383","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

Immunoproteasome as a biomarker for immunotherapy 作为免疫疗法生物标志物的免疫蛋白酶体

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-15 DOI: 10.1038/s41568-024-00759-7

Radhakrishnan Sabarinathan

引用次数: 0

Encoding spatial tumour dynamics with Starfysh 用 Starfysh 对空间肿瘤动态进行编码

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-11 DOI: 10.1038/s41568-024-00764-w

Siyu He

引用次数: 0

Compressive stresses in cancer: characterization and implications for tumour progression and treatment 癌症中的压缩应力：特征描述及其对肿瘤进展和治疗的影响

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-10 DOI: 10.1038/s41568-024-00745-z

Julia A. Linke, Lance L. Munn, Rakesh K. Jain

{"title":"Compressive stresses in cancer: characterization and implications for tumour progression and treatment","authors":"Julia A. Linke, Lance L. Munn, Rakesh K. Jain","doi":"10.1038/s41568-024-00745-z","DOIUrl":"10.1038/s41568-024-00745-z","url":null,"abstract":"Beyond their many well-established biological aberrations, solid tumours create an abnormal physical microenvironment that fuels cancer progression and confers treatment resistance. Mechanical forces impact tumours across a range of biological sizes and timescales, from rapid events at the molecular level involved in their sensing and transmission, to slower and larger-scale events, including clonal selection, epigenetic changes, cell invasion, metastasis and immune response. Owing to challenges with studying these dynamic stimuli in biological systems, the mechanistic understanding of the effects and pathways triggered by abnormally elevated mechanical forces remains elusive, despite clear correlations with cancer pathophysiology, aggressiveness and therapeutic resistance. In this Review, we examine the emerging and diverse roles of physical forces in solid tumours and provide a comprehensive framework for understanding solid stress mechanobiology. We first review the physiological importance of mechanical forces, especially compressive stresses, and discuss their defining characteristics, biological context and relative magnitudes. We then explain how abnormal compressive stresses emerge in tumours and describe the experimental challenges in investigating these mechanically induced processes. Finally, we discuss the clinical translation of mechanotherapeutics that alleviate solid stresses and their potential to synergize with chemotherapy, radiotherapy and immunotherapies. In this Review, Linke, Munn and Jain provide a framework for understanding solid stress mechanobiology, examine the emerging and diverse roles of elevated compressive stresses in solid tumours, and highlight the potential for targeting mechanical abnormalities in cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 11","pages":"768-791"},"PeriodicalIF":72.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397861","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

Male melanoma comes of age 男性黑色素瘤进入成熟期

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-10 DOI: 10.1038/s41568-024-00766-8

Daniela Senft

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Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells 癌症诱导的远处器官系统性预处理：为转移细胞建立生态位

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-10-10 DOI: 10.1038/s41568-024-00752-0

Nicolas Rabas, Rute M. M. Ferreira, Stefania Di Blasio, Ilaria Malanchi

{"title":"Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells","authors":"Nicolas Rabas, Rute M. M. Ferreira, Stefania Di Blasio, Ilaria Malanchi","doi":"10.1038/s41568-024-00752-0","DOIUrl":"10.1038/s41568-024-00752-0","url":null,"abstract":"From their early genesis, tumour cells integrate with the surrounding normal cells to form an abnormal structure that is tightly integrated with the host organism via blood and lymphatic vessels and even neural associations. Using these connections, emerging cancers send a plethora of mediators that efficiently perturb the entire organism and induce changes in distant tissues. These perturbations serendipitously favour early metastatic establishment by promoting a more favourable tissue environment (niche) that supports the persistence of disseminated tumour cells within a foreign tissue. Because the establishment of early metastatic niches represents a key limiting step for metastasis, the creation of a more suitable pre-conditioned tissue strongly enhances metastatic success. In this Review, we provide an updated view of the mechanisms and mediators of primary tumours described so far that induce a pro-metastatic conditioning of distant organs, which favours early metastatic niche formation. We reflect on the nature of cancer-induced systemic conditioning, considering that non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning. We argue that a more holistic view of the processes catalysing metastatic progression is needed to identify preventive or therapeutic opportunities. In this Review, Rabas et al. describe the mechanisms by which primary tumours precondition distal organs to favour metastatic colonization — a limiting step of metastasis — and discuss how non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning, emphasizing the need for a holistic view to identify preventive or therapeutic opportunities.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"829-849"},"PeriodicalIF":72.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397859","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