Pub Date : 2026-01-23DOI: 10.1038/s41577-026-01266-6
Jaroslav Zak,John R Teijaro
JAK inhibitors target a large group of cytokines that signal through the JAK-STAT pathway and are typically used clinically as immunosuppressive agents. However, recent work has demonstrated the paradoxical ability of JAK inhibitors to enhance antitumour and antiviral immune responses and established their synergy with immune checkpoint inhibitors in early-stage clinical trials. In this Perspective, we consider why JAK inhibitors, which are typically used as immunosuppressive drugs, can have immune-enhancing effects, exploring the potential mechanistic basis and the opportunities to harness this effect to improve cancer immunotherapy.
{"title":"Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy.","authors":"Jaroslav Zak,John R Teijaro","doi":"10.1038/s41577-026-01266-6","DOIUrl":"https://doi.org/10.1038/s41577-026-01266-6","url":null,"abstract":"JAK inhibitors target a large group of cytokines that signal through the JAK-STAT pathway and are typically used clinically as immunosuppressive agents. However, recent work has demonstrated the paradoxical ability of JAK inhibitors to enhance antitumour and antiviral immune responses and established their synergy with immune checkpoint inhibitors in early-stage clinical trials. In this Perspective, we consider why JAK inhibitors, which are typically used as immunosuppressive drugs, can have immune-enhancing effects, exploring the potential mechanistic basis and the opportunities to harness this effect to improve cancer immunotherapy.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"186 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033855","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 : 2026-01-21DOI: 10.1038/s41577-025-01262-2
Noa B Martín-Cófreces,Diego Calzada-Fraile,Francisco Sánchez-Madrid
In the context of adaptive immunity, T cells are activated by professional antigen-presenting cells (APCs) in a process that begins with peptide-MHC complexes on the APC being recognized by T cell receptor and CD3 co-receptor complexes on the T cell. This triggers a reorganization of T cell morphology, formation of an immune synapse, and the delivery of signals that ultimately culminate in nuclear activation. The interaction between T cells and APCs, such as dendritic cells (DCs), was originally viewed as a unidirectional information highway in which the APC instructs the T cell. It is now clear that bidirectional crosstalk occurs at the immune synapse and that T cells also shape APC functions. The concept of 'DC licensing' originally suggested an instructive role for T cells in modifying DC functions. More recent studies have provided important insight into the changes that occur in DCs during antigen-driven contacts with T cells at the immune synapse. In this Review, we discuss our current understanding of the bidirectional T cell-DC crosstalk that occurs at the IS and its relevance for immune responses and immunotherapies.
{"title":"How crosstalk at the immune synapse shapes T cell and dendritic cell biologys.","authors":"Noa B Martín-Cófreces,Diego Calzada-Fraile,Francisco Sánchez-Madrid","doi":"10.1038/s41577-025-01262-2","DOIUrl":"https://doi.org/10.1038/s41577-025-01262-2","url":null,"abstract":"In the context of adaptive immunity, T cells are activated by professional antigen-presenting cells (APCs) in a process that begins with peptide-MHC complexes on the APC being recognized by T cell receptor and CD3 co-receptor complexes on the T cell. This triggers a reorganization of T cell morphology, formation of an immune synapse, and the delivery of signals that ultimately culminate in nuclear activation. The interaction between T cells and APCs, such as dendritic cells (DCs), was originally viewed as a unidirectional information highway in which the APC instructs the T cell. It is now clear that bidirectional crosstalk occurs at the immune synapse and that T cells also shape APC functions. The concept of 'DC licensing' originally suggested an instructive role for T cells in modifying DC functions. More recent studies have provided important insight into the changes that occur in DCs during antigen-driven contacts with T cells at the immune synapse. In this Review, we discuss our current understanding of the bidirectional T cell-DC crosstalk that occurs at the IS and its relevance for immune responses and immunotherapies.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"258 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015330","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 : 2026-01-19DOI: 10.1038/s41577-026-01272-8
Lucy Bird
A new study shows that inflammation spreads from psoriatic skin to joint disease through the migration of skin myeloid precursors to the joints, where they can become inflammatory macrophages unless they are kept in check by resident regulatory fibroblasts.
{"title":"Spreading inflammation via the skin–joint axis","authors":"Lucy Bird","doi":"10.1038/s41577-026-01272-8","DOIUrl":"10.1038/s41577-026-01272-8","url":null,"abstract":"A new study shows that inflammation spreads from psoriatic skin to joint disease through the migration of skin myeloid precursors to the joints, where they can become inflammatory macrophages unless they are kept in check by resident regulatory fibroblasts.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 2","pages":"85-85"},"PeriodicalIF":60.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003913","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 : 2026-01-16DOI: 10.1038/s41577-026-01271-9
Alexandra Flemming
Respiratory viral infections can weaken the immune system and carry a risk of severe bacterial secondary infections. A research article in Science Immunology shows that segmented filamentous bacteria in the gut can enhance the antibacterial function of alveolar macrophages in the lungs and provide protection against secondary infections.
{"title":"Segmented filamentous bacteria in the gut protect against secondary bacterial infections in the lung","authors":"Alexandra Flemming","doi":"10.1038/s41577-026-01271-9","DOIUrl":"10.1038/s41577-026-01271-9","url":null,"abstract":"Respiratory viral infections can weaken the immune system and carry a risk of severe bacterial secondary infections. A research article in Science Immunology shows that segmented filamentous bacteria in the gut can enhance the antibacterial function of alveolar macrophages in the lungs and provide protection against secondary infections.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 2","pages":"86-86"},"PeriodicalIF":60.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986526","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 : 2026-01-15DOI: 10.1038/s41577-025-01254-2
Martin Turner,Georg Petkau
Infection triggers one of the most dramatic systemic responses in the body, and the coordinated activation and function of immune cells requires a dynamic regulation of transcriptomes and proteomes. This is achieved by RNA-binding proteins, which, together with RNA, form ribonucleoproteins. These proteins expand the information content of the genome and determine the lifespan, localization and function of RNA. Moreover, they control when, where and how much protein is produced. They can also mediate cell-autonomous immunity to foreign RNA and to misfolded self-RNAs and ensure the fidelity of the transcriptome by acting as RNA modifiers and chaperones to prevent RNA misfolding. These activities are integrated with gene expression programmes that are induced by the pathogen-sensing mechanisms of immune cells, which together activate, and later resolve, immune responses. Here, we review the activities of RNA-binding proteins in immune cells and discuss how perturbations of their function can result in immunodeficiency, autoimmunity and chronic inflammation.
{"title":"RNA-binding proteins and ribonucleoproteins as determinants of immunity.","authors":"Martin Turner,Georg Petkau","doi":"10.1038/s41577-025-01254-2","DOIUrl":"https://doi.org/10.1038/s41577-025-01254-2","url":null,"abstract":"Infection triggers one of the most dramatic systemic responses in the body, and the coordinated activation and function of immune cells requires a dynamic regulation of transcriptomes and proteomes. This is achieved by RNA-binding proteins, which, together with RNA, form ribonucleoproteins. These proteins expand the information content of the genome and determine the lifespan, localization and function of RNA. Moreover, they control when, where and how much protein is produced. They can also mediate cell-autonomous immunity to foreign RNA and to misfolded self-RNAs and ensure the fidelity of the transcriptome by acting as RNA modifiers and chaperones to prevent RNA misfolding. These activities are integrated with gene expression programmes that are induced by the pathogen-sensing mechanisms of immune cells, which together activate, and later resolve, immune responses. Here, we review the activities of RNA-binding proteins in immune cells and discuss how perturbations of their function can result in immunodeficiency, autoimmunity and chronic inflammation.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"20 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986529","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 : 2026-01-14DOI: 10.1038/s41577-026-01267-5
Kirsty Minton
A study by Liu et al. identifies GPX4 as an immunosuppressive mediator released by ferroptotic tumour cells that inhibits the antitumour response.
Liu等人的研究发现GPX4是一种由嗜铁性肿瘤细胞释放的抑制抗肿瘤反应的免疫抑制介质。
{"title":"Ferroptotic tumour cells inhibit dendritic cell maturation through GPX4 release","authors":"Kirsty Minton","doi":"10.1038/s41577-026-01267-5","DOIUrl":"10.1038/s41577-026-01267-5","url":null,"abstract":"A study by Liu et al. identifies GPX4 as an immunosuppressive mediator released by ferroptotic tumour cells that inhibits the antitumour response.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 2","pages":"83-83"},"PeriodicalIF":60.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968534","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 : 2026-01-12DOI: 10.1038/s41577-026-01265-7
Frederika Rentzeperis, Brian Kim
A preprint by Zhu et al. shows that protease allergens induce neural hypersensitivity by activating mTORC1 signalling in sensory neurons.
Zhu等人的预印本表明，蛋白酶过敏原通过激活感觉神经元中的mTORC1信号诱导神经过敏。
{"title":"Sensory neurons promote allergic sensitization and cross-sensitization via mTORC1","authors":"Frederika Rentzeperis, Brian Kim","doi":"10.1038/s41577-026-01265-7","DOIUrl":"10.1038/s41577-026-01265-7","url":null,"abstract":"A preprint by Zhu et al. shows that protease allergens induce neural hypersensitivity by activating mTORC1 signalling in sensory neurons.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 2","pages":"88-88"},"PeriodicalIF":60.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955486","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 : 2026-01-12DOI: 10.1038/s41577-025-01258-y
Youxiang Mao,Wenjun Xia,Peng Jiang
Alterations in key metabolic pathways are required for tumour development and the adaptation of tumour cells to intrinsic or extrinsic stresses, as well as for the regulation of immune cell fate and immune responses in the tumour microenvironment. In particular, the dysregulation or alteration of certain metabolites produced by tumour cells has been shown to be important in creating the immunosuppressive tumour microenvironment. Recent studies have broadened our understanding of the interactions between metabolites and antitumour immunity. Here we highlight how, beyond their metabolic role, metabolites can function as signalling molecules to modulate the behaviours of immune cells and tumour cells. We also discuss potential therapeutic strategies targeting specific metabolites and future research directions in metabolite sensing.
{"title":"Metabolites as signalling molecules in the tumour immune microenvironment.","authors":"Youxiang Mao,Wenjun Xia,Peng Jiang","doi":"10.1038/s41577-025-01258-y","DOIUrl":"https://doi.org/10.1038/s41577-025-01258-y","url":null,"abstract":"Alterations in key metabolic pathways are required for tumour development and the adaptation of tumour cells to intrinsic or extrinsic stresses, as well as for the regulation of immune cell fate and immune responses in the tumour microenvironment. In particular, the dysregulation or alteration of certain metabolites produced by tumour cells has been shown to be important in creating the immunosuppressive tumour microenvironment. Recent studies have broadened our understanding of the interactions between metabolites and antitumour immunity. Here we highlight how, beyond their metabolic role, metabolites can function as signalling molecules to modulate the behaviours of immune cells and tumour cells. We also discuss potential therapeutic strategies targeting specific metabolites and future research directions in metabolite sensing.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"248 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955488","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 : 2026-01-12DOI: 10.1038/s41577-026-01270-w
Yvonne Bordon
Serum albumin binds and prevents the oxidation of free fatty acids, which then prevent the expression of virulence factors in Mucorales fungi.
血清白蛋白结合并阻止游离脂肪酸的氧化，从而阻止Mucorales真菌毒力因子的表达。
{"title":"Albumin protects against deadly fungal infection","authors":"Yvonne Bordon","doi":"10.1038/s41577-026-01270-w","DOIUrl":"10.1038/s41577-026-01270-w","url":null,"abstract":"Serum albumin binds and prevents the oxidation of free fatty acids, which then prevent the expression of virulence factors in Mucorales fungi.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 2","pages":"84-84"},"PeriodicalIF":60.9,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955487","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 : 2026-01-09DOI: 10.1038/s41577-026-01264-8
Emery Hoos, Malcolm J. W. Sim
A preprint by McCarron et al. investigates immunodominance hierarchies in response to cancer vaccines targeting neoantigens.
McCarron等人的预印本研究了针对新抗原的癌症疫苗的免疫优势等级反应。
{"title":"T cell competition in multi-neoantigen cancer vaccines","authors":"Emery Hoos, Malcolm J. W. Sim","doi":"10.1038/s41577-026-01264-8","DOIUrl":"10.1038/s41577-026-01264-8","url":null,"abstract":"A preprint by McCarron et al. investigates immunodominance hierarchies in response to cancer vaccines targeting neoantigens.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"26 2","pages":"88-88"},"PeriodicalIF":60.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937783","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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