Pub Date : 2024-05-02DOI: 10.1038/s41577-024-01030-8
Tim R. Mosmann, Andrew J. McMichael, Alexandre LeVert, John W. McCauley, Jeffrey W. Almond
Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza. Thus, future vaccines designed to promote both broad T cell effector functions and antibodies may provide enhanced protection. As we discuss, such vaccines present several challenges that require new strategic and economic considerations. Vaccine-induced T cells relevant to protection may reside in the lungs or lymphoid tissues, requiring more invasive assays to assess the immunogenicity of vaccine candidates. T cell functions may contain and resolve infection rather than completely prevent infection and early illness, requiring vaccine effectiveness to be assessed based on the prevention of severe disease and death rather than symptomatic infection. It can be complex and costly to measure T cell responses and infrequent clinical outcomes, and thus innovations in clinical trial design are needed for economic reasons. Nevertheless, the goal of more effective influenza vaccines justifies renewed and intensive efforts.
疫苗接种仍然是我们抵御流感的主要手段，流感每年造成大量死亡，并构成严重的大流行威胁。流感病毒通过迅速改变其表面抗原来逃避免疫，但即使疫苗与当前流行的病毒株非常匹配，流感疫苗也不如许多其他疫苗有效。流感疫苗的研发历来侧重于诱导保护性抗体，但越来越多的证据表明，T 细胞反应也对流感有保护作用。因此，未来旨在促进广泛的 T 细胞效应功能和抗体的疫苗可能会提供更强的保护。正如我们所讨论的，这类疫苗面临着一些挑战，需要新的战略和经济考量。疫苗诱导的与保护相关的 T 细胞可能存在于肺部或淋巴组织中，因此需要更多侵入性试验来评估候选疫苗的免疫原性。T 细胞功能可能会抑制和化解感染，而不是完全预防感染和早期疾病，这就要求根据预防严重疾病和死亡而不是无症状感染来评估疫苗的有效性。对 T 细胞反应和不常见的临床结果进行测量既复杂又昂贵，因此出于经济原因，需要对临床试验设计进行创新。尽管如此，为了实现更有效的流感疫苗这一目标，我们有理由继续加紧努力。
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Pub Date : 2024-04-29DOI: 10.1038/s41577-024-01027-3
Yi Huang, Wei Jiang, Rongbin Zhou
Damage-associated molecular patterns (DAMPs) are endogenous molecules that are released from host cells as a result of cell death or damage. The release of DAMPs in tissues is associated with loss of tissue homeostasis. Sensing of DAMPs by innate immune receptors triggers inflammation, which can be beneficial in initiating the processes that restore tissue homeostasis but can also drive inflammatory diseases. In recent years, the sensing of intracellular DAMPs has received extensive attention in the field of sterile inflammation. However, emerging studies have shown that DAMPs that originate from neighbouring cells, and even from distal tissues or organs, also mediate sterile inflammatory responses. This multi-level sensing of DAMPs is crucial for intercellular, trans-tissue and trans-organ communication. Here, we summarize how DAMP-sensing receptors detect DAMPs from intracellular, intercellular or distal tissue and organ sources to mediate sterile inflammation. We also discuss the possibility of targeting DAMPs or their corresponding receptors to treat inflammatory diseases.
{"title":"DAMP sensing and sterile inflammation: intracellular, intercellular and inter-organ pathways","authors":"Yi Huang, Wei Jiang, Rongbin Zhou","doi":"10.1038/s41577-024-01027-3","DOIUrl":"https://doi.org/10.1038/s41577-024-01027-3","url":null,"abstract":"<p>Damage-associated molecular patterns (DAMPs) are endogenous molecules that are released from host cells as a result of cell death or damage. The release of DAMPs in tissues is associated with loss of tissue homeostasis. Sensing of DAMPs by innate immune receptors triggers inflammation, which can be beneficial in initiating the processes that restore tissue homeostasis but can also drive inflammatory diseases. In recent years, the sensing of intracellular DAMPs has received extensive attention in the field of sterile inflammation. However, emerging studies have shown that DAMPs that originate from neighbouring cells, and even from distal tissues or organs, also mediate sterile inflammatory responses. This multi-level sensing of DAMPs is crucial for intercellular, trans-tissue and trans-organ communication. Here, we summarize how DAMP-sensing receptors detect DAMPs from intracellular, intercellular or distal tissue and organ sources to mediate sterile inflammation. We also discuss the possibility of targeting DAMPs or their corresponding receptors to treat inflammatory diseases.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814463","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 : 2024-04-26DOI: 10.1038/s41577-024-01038-0
Robyn Loves, Eyal Grunebaum
A preprint by Yi et al. shows a role for the FAS signalling pathway in controlling the persistence of CAR-modified lymphocytes.
Yi等人的预印本显示了FAS信号通路在控制CAR修饰淋巴细胞的持久性方面的作用。
{"title":"FAS signalling pathway is crucial for CAR T cell persistence","authors":"Robyn Loves, Eyal Grunebaum","doi":"10.1038/s41577-024-01038-0","DOIUrl":"10.1038/s41577-024-01038-0","url":null,"abstract":"A preprint by Yi et al. shows a role for the FAS signalling pathway in controlling the persistence of CAR-modified lymphocytes.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648700","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 : 2024-04-26DOI: 10.1038/s41577-024-01039-z
Kirsty Minton
Wei et al. report a role for membrane perforation mediated by gasdermin D pores in disruption of the blood–brain barrier.
Wei 等人报告了由气孔 D 介导的膜穿孔在破坏血脑屏障中的作用。
{"title":"Noncanonical inflammasome mediates BBB breakdown","authors":"Kirsty Minton","doi":"10.1038/s41577-024-01039-z","DOIUrl":"10.1038/s41577-024-01039-z","url":null,"abstract":"Wei et al. report a role for membrane perforation mediated by gasdermin D pores in disruption of the blood–brain barrier.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648777","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 : 2024-04-24DOI: 10.1038/s41577-024-01022-8
Karen E. Martin, Quirin Hammer, Karlo Perica, Michel Sadelain, Karl-Johan Malmberg
Allogeneic cellular immunotherapies hold a great promise for cancer treatment owing to their potential cost-effectiveness, scalability and on-demand availability. However, immune rejection of adoptively transferred allogeneic T and natural killer (NK) cells is a substantial obstacle to achieving clinical responses that are comparable to responses obtained with current autologous chimeric antigen receptor T cell therapies. In this Perspective, we discuss strategies to confer cell-intrinsic, immune-evasive properties to allogeneic T cells and NK cells in order to prevent or delay their immune rejection, thereby widening the therapeutic window. We discuss how common viral and cancer immune escape mechanisms can serve as a blueprint for improving the persistence of off-the-shelf allogeneic cell therapies. The prospects of harnessing genome editing and synthetic biology to design cell-based precision immunotherapies extend beyond programming target specificities and require careful consideration of innate and adaptive responses in the recipient that may curtail the biodistribution, in vivo expansion and persistence of cellular therapeutics. Genome editing approaches can be used to confer immune-evasive properties to allogeneic cellular immunotherapies, with the aim of achieving persistent responses and efficiencies that are comparable to those of autologous chimeric antigen receptor T cell therapies. This Perspective discusses how current knowledge about viral or tumour immune evasion could be incorporated into the design of off-the-shelf tumour-specific T and NK cells for the production of cost-effective and scalable cancer immunotherapies.
{"title":"Engineering immune-evasive allogeneic cellular immunotherapies","authors":"Karen E. Martin, Quirin Hammer, Karlo Perica, Michel Sadelain, Karl-Johan Malmberg","doi":"10.1038/s41577-024-01022-8","DOIUrl":"10.1038/s41577-024-01022-8","url":null,"abstract":"Allogeneic cellular immunotherapies hold a great promise for cancer treatment owing to their potential cost-effectiveness, scalability and on-demand availability. However, immune rejection of adoptively transferred allogeneic T and natural killer (NK) cells is a substantial obstacle to achieving clinical responses that are comparable to responses obtained with current autologous chimeric antigen receptor T cell therapies. In this Perspective, we discuss strategies to confer cell-intrinsic, immune-evasive properties to allogeneic T cells and NK cells in order to prevent or delay their immune rejection, thereby widening the therapeutic window. We discuss how common viral and cancer immune escape mechanisms can serve as a blueprint for improving the persistence of off-the-shelf allogeneic cell therapies. The prospects of harnessing genome editing and synthetic biology to design cell-based precision immunotherapies extend beyond programming target specificities and require careful consideration of innate and adaptive responses in the recipient that may curtail the biodistribution, in vivo expansion and persistence of cellular therapeutics. Genome editing approaches can be used to confer immune-evasive properties to allogeneic cellular immunotherapies, with the aim of achieving persistent responses and efficiencies that are comparable to those of autologous chimeric antigen receptor T cell therapies. This Perspective discusses how current knowledge about viral or tumour immune evasion could be incorporated into the design of off-the-shelf tumour-specific T and NK cells for the production of cost-effective and scalable cancer immunotherapies.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639949","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 : 2024-04-24DOI: 10.1038/s41577-024-01036-2
Lucy Bird
Sex hormones in male mice negatively regulate type 2 innate lymphoid cells in the skin, impairing the induction and activation of dendritic cells and thereby contributing to differences in immunity in males and females.
{"title":"Weaker skin immunity in males due to androgen effects on ILC2s","authors":"Lucy Bird","doi":"10.1038/s41577-024-01036-2","DOIUrl":"10.1038/s41577-024-01036-2","url":null,"abstract":"Sex hormones in male mice negatively regulate type 2 innate lymphoid cells in the skin, impairing the induction and activation of dendritic cells and thereby contributing to differences in immunity in males and females.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639738","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 : 2024-04-24DOI: 10.1038/s41577-024-01037-1
Adrian Liston
Adrian Liston, professor of pathology at the University of Cambridge, UK, has published several illustrated children’s books on the topic of vaccination and has developed a computer game called ‘VirusFighter’. Here, he shares his thoughts on how to become an effective science communicator.
{"title":"Harnessing our lived experience for science communication","authors":"Adrian Liston","doi":"10.1038/s41577-024-01037-1","DOIUrl":"10.1038/s41577-024-01037-1","url":null,"abstract":"Adrian Liston, professor of pathology at the University of Cambridge, UK, has published several illustrated children’s books on the topic of vaccination and has developed a computer game called ‘VirusFighter’. Here, he shares his thoughts on how to become an effective science communicator.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":100.3,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639886","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 : 2024-04-22DOI: 10.1038/s41577-024-01026-4
Mara De Martino, Jeffrey C. Rathmell, Lorenzo Galluzzi, Claire Vanpouille-Box
Accumulating evidence suggests that metabolic rewiring in malignant cells supports tumour progression not only by providing cancer cells with increased proliferative potential and an improved ability to adapt to adverse microenvironmental conditions but also by favouring the evasion of natural and therapy-driven antitumour immune responses. Here, we review cancer cell-intrinsic and cancer cell-extrinsic mechanisms through which alterations of metabolism in malignant cells interfere with innate and adaptive immune functions in support of accelerated disease progression. Further, we discuss the potential of targeting such alterations to enhance anticancer immunity for therapeutic purposes. This Review discusses the mechanisms by which common alterations of cancer cell metabolism interfere with immune functions to promote immunoevasion and tumour progression, and avenues to target such alterations for therapeutic purposes.
{"title":"Cancer cell metabolism and antitumour immunity","authors":"Mara De Martino, Jeffrey C. Rathmell, Lorenzo Galluzzi, Claire Vanpouille-Box","doi":"10.1038/s41577-024-01026-4","DOIUrl":"10.1038/s41577-024-01026-4","url":null,"abstract":"Accumulating evidence suggests that metabolic rewiring in malignant cells supports tumour progression not only by providing cancer cells with increased proliferative potential and an improved ability to adapt to adverse microenvironmental conditions but also by favouring the evasion of natural and therapy-driven antitumour immune responses. Here, we review cancer cell-intrinsic and cancer cell-extrinsic mechanisms through which alterations of metabolism in malignant cells interfere with innate and adaptive immune functions in support of accelerated disease progression. Further, we discuss the potential of targeting such alterations to enhance anticancer immunity for therapeutic purposes. This Review discusses the mechanisms by which common alterations of cancer cell metabolism interfere with immune functions to promote immunoevasion and tumour progression, and avenues to target such alterations for therapeutic purposes.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":null,"pages":null},"PeriodicalIF":67.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637553","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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