Pub Date : 2024-07-29DOI: 10.1038/s41577-024-01069-7
Qirong Lin, Kim Thrane, Camilla Engblom
In this Tools of the Trade article, Camilla Engblom and colleagues describe their elegant technique ‘Spatial VDJ’ to detect and map antigen receptor sequences in human tissue sections.
{"title":"Location matters: mapping antigen receptors within tissues","authors":"Qirong Lin, Kim Thrane, Camilla Engblom","doi":"10.1038/s41577-024-01069-7","DOIUrl":"10.1038/s41577-024-01069-7","url":null,"abstract":"In this Tools of the Trade article, Camilla Engblom and colleagues describe their elegant technique ‘Spatial VDJ’ to detect and map antigen receptor sequences in human tissue sections.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"617-617"},"PeriodicalIF":67.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791028","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 : 2024-07-25DOI: 10.1038/s41577-024-01061-1
Michael T. Lotze, Scott H. Olejniczak, Dimitris Skokos
Substantial progress in understanding T cell signalling, particularly with respect to T cell co-receptors such as the co-stimulatory receptor CD28, has been made in recent years. This knowledge has been instrumental in the development of innovative immunotherapies for patients with cancer, including immune checkpoint blockade antibodies, adoptive cell therapies, tumour-targeted immunostimulatory antibodies, and immunostimulatory small-molecule drugs that regulate T cell activation. Following the failed clinical trial of a CD28 superagonist antibody in 2006, targeted CD28 agonism has re-emerged as a technologically viable and clinically promising strategy for cancer immunotherapy. In this Review, we explore recent insights into the molecular functions and regulation of CD28. We describe how CD28 is central to the success of current cancer immunotherapies and examine how new questions arising from studies of CD28 as a clinical target have enhanced our understanding of its biological role and may guide the development of future therapeutic strategies in oncology. This Review covers recent advances in our understanding of CD28 co-stimulation of T cells and discusses an emerging paradigm that positions CD28 as central to the success of current and future immunotherapeutic approaches to treating cancer.
近年来，人们在了解 T 细胞信号，特别是 T 细胞共受体（如共刺激受体 CD28）方面取得了重大进展。这些知识有助于为癌症患者开发创新的免疫疗法，包括免疫检查点阻断抗体、收养细胞疗法、肿瘤靶向免疫刺激抗体和调节 T 细胞活化的免疫刺激小分子药物。继2006年CD28超拮抗剂抗体的临床试验失败后，靶向CD28激动剂作为一种技术上可行、临床上有前景的癌症免疫疗法策略重新崛起。在本综述中，我们将探讨 CD28 分子功能和调控的最新研究成果。我们描述了 CD28 如何成为当前癌症免疫疗法成功的核心，并探讨了将 CD28 作为临床靶点的研究中出现的新问题如何增进了我们对其生物学作用的了解，以及如何指导未来肿瘤学治疗策略的开发。
{"title":"CD28 co-stimulation: novel insights and applications in cancer immunotherapy","authors":"Michael T. Lotze, Scott H. Olejniczak, Dimitris Skokos","doi":"10.1038/s41577-024-01061-1","DOIUrl":"10.1038/s41577-024-01061-1","url":null,"abstract":"Substantial progress in understanding T cell signalling, particularly with respect to T cell co-receptors such as the co-stimulatory receptor CD28, has been made in recent years. This knowledge has been instrumental in the development of innovative immunotherapies for patients with cancer, including immune checkpoint blockade antibodies, adoptive cell therapies, tumour-targeted immunostimulatory antibodies, and immunostimulatory small-molecule drugs that regulate T cell activation. Following the failed clinical trial of a CD28 superagonist antibody in 2006, targeted CD28 agonism has re-emerged as a technologically viable and clinically promising strategy for cancer immunotherapy. In this Review, we explore recent insights into the molecular functions and regulation of CD28. We describe how CD28 is central to the success of current cancer immunotherapies and examine how new questions arising from studies of CD28 as a clinical target have enhanced our understanding of its biological role and may guide the development of future therapeutic strategies in oncology. This Review covers recent advances in our understanding of CD28 co-stimulation of T cells and discusses an emerging paradigm that positions CD28 as central to the success of current and future immunotherapeutic approaches to treating cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 12","pages":"878-895"},"PeriodicalIF":67.7,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759985","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 : 2024-07-15DOI: 10.1038/s41577-024-01057-x
Michael H. Lee, Sean-Paul Nuccio, Ipsita Mohanty, Lee R. Hagey, Pieter C. Dorrestein, Hiutung Chu, Manuela Raffatellu
Bile acids are increasingly appearing in the spotlight owing to their novel impacts on various host processes. Similarly, there is growing attention on members of the microbiota that are responsible for bile acid modifications. With recent advances in technology enabling the discovery and continued identification of microbially conjugated bile acids, the chemical complexity of the bile acid landscape in the body is increasing at a rapid pace. In this Review, we summarize our current understanding of how bile acids and the gut microbiota interact to modulate immune responses during homeostasis and disease, with a particular focus on the gut. Here, Raffatellu and co-workers discuss our growing understanding of how primary bile acids (which are cholesterol-derived molecules synthesized in the liver) and secondary bile acids (which are primary bile acids that have been microbially modified) shape immune responses in health and disease, with a particular focus on bile acids and intestinal immunity.
{"title":"How bile acids and the microbiota interact to shape host immunity","authors":"Michael H. Lee, Sean-Paul Nuccio, Ipsita Mohanty, Lee R. Hagey, Pieter C. Dorrestein, Hiutung Chu, Manuela Raffatellu","doi":"10.1038/s41577-024-01057-x","DOIUrl":"10.1038/s41577-024-01057-x","url":null,"abstract":"Bile acids are increasingly appearing in the spotlight owing to their novel impacts on various host processes. Similarly, there is growing attention on members of the microbiota that are responsible for bile acid modifications. With recent advances in technology enabling the discovery and continued identification of microbially conjugated bile acids, the chemical complexity of the bile acid landscape in the body is increasing at a rapid pace. In this Review, we summarize our current understanding of how bile acids and the gut microbiota interact to modulate immune responses during homeostasis and disease, with a particular focus on the gut. Here, Raffatellu and co-workers discuss our growing understanding of how primary bile acids (which are cholesterol-derived molecules synthesized in the liver) and secondary bile acids (which are primary bile acids that have been microbially modified) shape immune responses in health and disease, with a particular focus on bile acids and intestinal immunity.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"798-809"},"PeriodicalIF":67.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618200","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 : 2024-07-12DOI: 10.1038/s41577-024-01065-x
Lucy Bird
Age-associated defects in dendritic cells can be corrected by hyperactivating adjuvants containing an oxidized phospholipid to induce effective antitumour responses in mice.
{"title":"Elixir for DCs","authors":"Lucy Bird","doi":"10.1038/s41577-024-01065-x","DOIUrl":"10.1038/s41577-024-01065-x","url":null,"abstract":"Age-associated defects in dendritic cells can be corrected by hyperactivating adjuvants containing an oxidized phospholipid to induce effective antitumour responses in mice.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"540-540"},"PeriodicalIF":67.7,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597353","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 : 2024-07-12DOI: 10.1038/s41577-024-01066-w
Nicolas Vabret, Jaime Mateus-Tique, Hélène Salmon, Jérôme C. Martin, Véronique Mateo, Sandra Serrano, François Lemoine, Roger Chammas, Miriam Merad
Online technologies for immunology education can facilitate global outreach, incorporate local expertise, promote inclusivity and mitigate environmental costs of international travel. The experience gained from ten years of Immunoschool demonstrates how an engaging format with active participation is crucial to achieving these goals. In this Comment article, organizers of the International School of Immunotherapy (Immunoschool) reflect on the experience gained from the past ten years in using online technologies for global and inclusive immunology education.
{"title":"Online immunology education for a global world","authors":"Nicolas Vabret, Jaime Mateus-Tique, Hélène Salmon, Jérôme C. Martin, Véronique Mateo, Sandra Serrano, François Lemoine, Roger Chammas, Miriam Merad","doi":"10.1038/s41577-024-01066-w","DOIUrl":"10.1038/s41577-024-01066-w","url":null,"abstract":"Online technologies for immunology education can facilitate global outreach, incorporate local expertise, promote inclusivity and mitigate environmental costs of international travel. The experience gained from ten years of Immunoschool demonstrates how an engaging format with active participation is crucial to achieving these goals. In this Comment article, organizers of the International School of Immunotherapy (Immunoschool) reflect on the experience gained from the past ten years in using online technologies for global and inclusive immunology education.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"615-616"},"PeriodicalIF":67.7,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597355","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":"Understanding NK cell heterogeneity","authors":"Alexandra Flemming","doi":"10.1038/s41577-024-01068-8","DOIUrl":"10.1038/s41577-024-01068-8","url":null,"abstract":"Two papers in Nature Immunology provide a comprehensive atlas of human natural killer cells in health and in different types of cancer.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"540-540"},"PeriodicalIF":67.7,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597354","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 : 2024-07-09DOI: 10.1038/s41577-024-01048-y
Isabelle C. Arnold, Ariel Munitz
Eosinophils are bone marrow-derived granulocytes that are traditionally associated with type 2 immune responses, such as those that occur during parasite infections and allergy. Emerging evidence demonstrates the remarkable functional plasticity of this elusive cell type and its pleiotropic functions in diverse settings. Eosinophils broadly contribute to tissue homeostasis, host defence and immune regulation, predominantly at mucosal sites. The scope of their activities primarily reflects the breadth of their portfolio of secreted mediators, which range from cytotoxic cationic proteins and reactive oxygen species to multiple cytokines, chemokines and lipid mediators. Here, we comprehensively review basic eosinophil biology that is directly related to their activities in homeostasis, protective immunity, regeneration and cancer. We examine how dysregulation of these functions contributes to the physiopathology of a broad range of inflammatory diseases. Furthermore, we discuss recent findings regarding the tissue compartmentalization and adaptation of eosinophils, shedding light on the factors that likely drive their functional diversification within tissues. This Review by Arnold and Munitz discusses the diverse roles of eosinophils in the settings of tissue homeostasis, infection, allergy and cancer. The authors explain the molecular mechanisms that enable eosinophils to adapt to diverse tissue types and conditions, and they consider the therapeutic potential of eosinophil-depleting drugs in the clinic.
{"title":"Spatial adaptation of eosinophils and their emerging roles in homeostasis, infection and disease","authors":"Isabelle C. Arnold, Ariel Munitz","doi":"10.1038/s41577-024-01048-y","DOIUrl":"10.1038/s41577-024-01048-y","url":null,"abstract":"Eosinophils are bone marrow-derived granulocytes that are traditionally associated with type 2 immune responses, such as those that occur during parasite infections and allergy. Emerging evidence demonstrates the remarkable functional plasticity of this elusive cell type and its pleiotropic functions in diverse settings. Eosinophils broadly contribute to tissue homeostasis, host defence and immune regulation, predominantly at mucosal sites. The scope of their activities primarily reflects the breadth of their portfolio of secreted mediators, which range from cytotoxic cationic proteins and reactive oxygen species to multiple cytokines, chemokines and lipid mediators. Here, we comprehensively review basic eosinophil biology that is directly related to their activities in homeostasis, protective immunity, regeneration and cancer. We examine how dysregulation of these functions contributes to the physiopathology of a broad range of inflammatory diseases. Furthermore, we discuss recent findings regarding the tissue compartmentalization and adaptation of eosinophils, shedding light on the factors that likely drive their functional diversification within tissues. This Review by Arnold and Munitz discusses the diverse roles of eosinophils in the settings of tissue homeostasis, infection, allergy and cancer. The authors explain the molecular mechanisms that enable eosinophils to adapt to diverse tissue types and conditions, and they consider the therapeutic potential of eosinophil-depleting drugs in the clinic.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 12","pages":"858-877"},"PeriodicalIF":67.7,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561317","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 : 2024-07-05DOI: 10.1038/s41577-024-01062-0
Leila Akkari, Ido Amit, Vincenzo Bronte, Zvi G. Fridlender, Dmitry I. Gabrilovich, Florent Ginhoux, Catherine C. Hedrick, Suzanne Ostrand-Rosenberg
Myeloid-derived suppressor cells (MDSCs) are cells of neutrophil and monocyte lineages with potent immunosuppressive activity. Numerous studies in mice and humans have identified important roles for MDSCs in suppressing the antitumour response and determining the efficacy of cancer immunotherapies. However, there is still much controversy regarding their identity, ontogeny and functions that must be resolved to fulfill their therapeutic potential. In this Viewpoint, Nature Reviews Immunology invites eight experts in the field to share their thoughts on the key questions and challenges in MDSC research. In this Viewpoint, Nature Reviews Immunology invites eight experts in the field to share their thoughts on the key questions and challenges in MDSC research.
{"title":"Defining myeloid-derived suppressor cells","authors":"Leila Akkari, Ido Amit, Vincenzo Bronte, Zvi G. Fridlender, Dmitry I. Gabrilovich, Florent Ginhoux, Catherine C. Hedrick, Suzanne Ostrand-Rosenberg","doi":"10.1038/s41577-024-01062-0","DOIUrl":"10.1038/s41577-024-01062-0","url":null,"abstract":"Myeloid-derived suppressor cells (MDSCs) are cells of neutrophil and monocyte lineages with potent immunosuppressive activity. Numerous studies in mice and humans have identified important roles for MDSCs in suppressing the antitumour response and determining the efficacy of cancer immunotherapies. However, there is still much controversy regarding their identity, ontogeny and functions that must be resolved to fulfill their therapeutic potential. In this Viewpoint, Nature Reviews Immunology invites eight experts in the field to share their thoughts on the key questions and challenges in MDSC research. In this Viewpoint, Nature Reviews Immunology invites eight experts in the field to share their thoughts on the key questions and challenges in MDSC research.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"24 12","pages":"850-857"},"PeriodicalIF":67.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538244","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":"Rethinking pDCs: a questionable ally in immunity?","authors":"Ester Gea-Mallorquí, Sarah Rowland-Jones","doi":"10.1038/s41577-024-01058-w","DOIUrl":"10.1038/s41577-024-01058-w","url":null,"abstract":"A preprint by Ngo et al. reports a new mouse model for the constitutive depletion of pDCs, showing that pDCs are dispensable for antiviral immunity.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":" ","pages":"542-542"},"PeriodicalIF":67.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534789","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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