Latest Reviews

  • Review Article |

    A transcription factor network triggered by Notch signalling in the thymus guides proliferating, multipotent progenitor cells into the T cell pathway. This Review describes how these factors work to establish regulatory target specificity, epigenomic impact and irreversibility for T cell identity.

    • Hiroyuki Hosokawa
    •  & Ellen V. Rothenberg
  • Review Article |

    Here, the authors explore how the modern way of life increases the risk of allergy and asthma, in particular by affecting the formation and diversity of the microbiota in early life. Understanding these changes highlights strategies for allergy prevention.

    • Harald Renz
    •  & Chrysanthi Skevaki
  • Viewpoint |

    For this Viewpoint, Nature Reviews Immunology asked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

    • Faith Osier
    • , Jenny P. Y. Ting
    • , John Fraser
    • , Bart N. Lambrecht
    • , Marta Romano
    • , Ricardo T. Gazzinelli
    • , Karina R. Bortoluci
    • , Dario S. Zamboni
    • , Arne N. Akbar
    • , Jennie Evans
    • , Doug E. Brown
    • , Kamala D. Patel
    • , Yuzhang Wu
    • , Ana B. Perez
    • , Oliver Pérez
    • , Thomas Kamradt
    • , Christine Falk
    • , Mira Barda-Saad
    • , Amiram Ariel
    • , Angela Santoni
    • , Francesco Annunziato
    • , Marco A. Cassatella
    • , Hiroshi Kiyono
    • , Valeriy Chereshnev
    • , Alioune Dieye
    • , Moustapha Mbow
    • , Babacar Mbengue
    • , Maguette D. S. Niang
    •  & Melinda Suchard
  • Review Article |

    Genetic models of dendritic cell (DC) development in mice have aided our understanding of the redundant and non-redundant functions of DC subsets and enabled translation of these findings to human DCs.

    • David A. Anderson III
    • , Charles-Antoine Dutertre
    • , Florent Ginhoux
    •  & Kenneth M. Murphy
  • Review Article |

    This Review outlines the guiding immunological principles for the design of coronavirus disease 2019 (COVID-19) vaccine strategies and analyses the current COVID-19 vaccine landscape and the challenges ahead.

    • Mangalakumari Jeyanathan
    • , Sam Afkhami
    • , Fiona Smaill
    • , Matthew S. Miller
    • , Brian D. Lichty
    •  & Zhou Xing
  • Review Article |

    Lactate accumulates in cancerous and chronically inflamed tissues, where it has diverse and often opposing effects. Here, the authors review the activities of this metabolite in these distinct circumstances, identifying opportunities for therapeutic modulation of the metabolic signature in tumours and inflammatory diseases.

    • Michelangelo Certo
    • , Chin-Hsien Tsai
    • , Valentina Pucino
    • , Ping-Chih Ho
    •  & Claudio Mauro
  • Review Article |

    In this Review, the authors describe how dysregulated protein translation in cancer cells is an important source of tumour-specific peptides for immunosurveillance and how MHC class I antigen-processing and presentation pathways are manipulated by tumours for immunoevasion — information that will inform cancer immunotherapy approaches.

    • Devin Dersh
    • , Jaroslav Hollý
    •  & Jonathan W. Yewdell
  • Review Article |

    In this Review, Rolls and colleagues discuss regulation of immune responses by the nervous system. The authors focus on the benefits of neuronal regulation of immunity, the mechanisms involved and the brain areas involved in neuro-immune crosstalk.

    • Maya Schiller
    • , Tamar L. Ben-Shaanan
    •  & Asya Rolls
  • Review Article |

    This Review covers our current understanding of the roles of IL-9-producing T cells in allergy and cancer. Should these cells be classified as a distinct IL-9-producing T helper cell subset? And can we therapeutically target them for the treatment of chronic allergic diseases and cancer?

    • Pornpimon Angkasekwinai
    •  & Chen Dong
  • Review Article |

    Antibody-dependent enhancement (ADE) has been described as a mechanism that contributes to the pathogenesis of dengue virus infection. Limited evidence also suggests that it can also occur in other viral infections. Here, the authors explore the history of the ADE phenomenon, discuss the diversity of Fc effector functions and consider its potential relevance in the context of SARS-CoV-2 infection.

    • Stylianos Bournazos
    • , Aaron Gupta
    •  & Jeffrey V. Ravetch
  • Review Article |

    Constitutive innate immune mechanisms, such as restriction factors, RNA interference, antimicrobial peptides, basal autophagy and proteasomal degradation, exert early host defence activities that also aim to minimize tissue damage and homeostatic disruption by limiting the activation of inducible innate immunity.

    • Søren R. Paludan
    • , Thomas Pradeu
    • , Seth L. Masters
    •  & Trine H. Mogensen
  • Review Article |

    Immunometabolism has a key role in HIV-1 pathogenesis, with the metabolic state of T cells and macrophages determining their susceptibility to infection, the metabolism of immune cells shaping their response to infection and metabolic products driving inflammation during infection.

    • Asier Sáez-Cirión
    •  & Irini Sereti
  • Progress |

    In this Progress article, Wang and Colonna highlight a flurry of recent reports that have shaped our understanding of how environmental cues and clock genes regulate group 3 innate lymphoid cells. They consider the implications of these findings for intestinal immunity.

    • Qianli Wang
    •  & Marco Colonna
  • Progress |

    In this Progress article, Zeyu Chen and E. John Wherry summarize early reports of the T cell responses observed in patients with COVID-19, emphasizing how different immune response characteristics in different patients may reflect a spectrum of disease phenotypes.

    • Zeyu Chen
    •  & E. John Wherry
  • Review Article |

    The ATP–adenosine pathway plays an important role in modulating innate and adaptive immune responses in the tumour microenvironment. Here, the authors focus on CD39, a key enzyme in the ATP–adenosine pathway, and examine immunotherapeutic strategies that target it.

    • Achim K. Moesta
    • , Xian-Yang Li
    •  & Mark J. Smyth
  • Viewpoint |

    In this Viewpoint, six leading experts consider the ways in which the microbiota can influence immune responses to cancer. Immunotherapies have been revolutionary in the treatment of cancer, but will we one day further increase their efficacy with microbiota-derived drugs?

    • B. Brett Finlay
    • , Romina Goldszmid
    • , Kenya Honda
    • , Giorgio Trinchieri
    • , Jennifer Wargo
    •  & Laurence Zitvogel
  • Perspective |

    Why does the human genome encode more than 300 potential immune inhibitory receptors? Here, the authors propose a categorization of inhibitory receptors — as threshold receptors and negative feedback receptors — that reflects their distinct functions in immune regulation, illustrated using mathematical modelling. This categorization may be useful for the therapeutic targeting of inhibitory receptors.

    • Matevž Rumpret
    • , Julia Drylewicz
    • , Laura J. E. Ackermans
    • , José A. M. Borghans
    • , Ruslan Medzhitov
    •  & Linde Meyaard
  • Review Article |

    The authors compare the thymic development of several innate-like T cell populations, including natural killer T cells, mucosal-associated invariant T cells and γδ T cells. They focus on the cytokines, surface molecules and transcription factors that are necessary for the development of these cells and highlight some of the key differences from conventional T cell development.

    • Daniel G. Pellicci
    • , Hui-Fern Koay
    •  & Stuart P. Berzins
  • Perspective |

    Recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) as well as antibodies targeted at GM-CSF or its receptor are being tested in clinical trials for coronavirus disease 2019 (COVID-19). This Perspective introduces the pleiotropic functions of GM-CSF and explores the rationale behind these different approaches.

    • Frederick M. Lang
    • , Kevin M.-C. Lee
    • , John R. Teijaro
    • , Burkhard Becher
    •  & John A. Hamilton
  • Perspective |

    Why are males more susceptible to severe COVID-19 than females? In this Perspective, Sabra Klein and colleagues consider the sex differences in the immune system that may contribute to this sex bias.

    • Eileen P. Scully
    • , Jenna Haverfield
    • , Rebecca L. Ursin
    • , Cara Tannenbaum
    •  & Sabra L. Klein
  • Perspective |

    The authors describe how the naive T cell compartment is built across a lifetime. They propose that functional diversity among naive T cells is linked to when they were created. Naive T cells adapt to meet changes in the external environment at different stages of life, persist into adulthood and contribute to the T cell compartment in adults.

    • Miles P. Davenport
    • , Norah L. Smith
    •  & Brian D. Rudd
  • Viewpoint |

    In this Viewpoint article, members of the Optimmunize consortium discuss the evidence for non-specific and sex-differential effects of vaccines and how this information might inform vaccine design and policy, including in relation to the COVID-19 pandemic.

    • Peter Aaby
    • , Christine Stabell Benn
    • , Katie L. Flanagan
    • , Sabra L. Klein
    • , Tobias R. Kollmann
    • , David J. Lynn
    •  & Frank Shann
  • Review Article |

    T cells play a central role in immune responses to cancer. In this guide to cancer immunotherapy, the authors provide a comprehensive historical and biological perspective on cancer immunotherapy, with a focus on current and emerging therapeutic approaches that harness T cells to fight cancer.

    • Alex D. Waldman
    • , Jill M. Fritz
    •  & Michael J. Lenardo
  • Review Article |

    Clonal expansion is no longer only the preserve of adaptive lymphocytes. Innate lymphocytes, in particular natural killer cells, also undergo clonal expansion in response to infection. Here, the authors compare and contrast this process for adaptive and innate lymphocytes.

    • Nicholas M. Adams
    • , Simon Grassmann
    •  & Joseph C. Sun
  • Progress |

    This Progress article from Merad and Martin examines our current understanding of the excessive inflammatory responses seen in patients with severe COVID-19. The authors focus on the emerging pathological roles of monocytes and macrophages and discuss the inflammatory pathways that are currently being targeted in the clinic.

    • Miriam Merad
    •  & Jerome C. Martin
  • Review Article |

    This Review from Gause, Rothlin and Loke considers how different layers of complexity influence the development of type 2 immunity. In particular, the discussion focuses on how variations in the initiating stimuli, tissue microenvironments and host genetics can lead to heterogeneity in type 2 immune responses.

    • William C. Gause
    • , Carla Rothlin
    •  & P’ng Loke
  • Review Article |

    The clinical activity of cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitors has largely been attributed to their capacity to block the proliferation of tumour cells, but increasing evidence discussed in this Review suggests that these inhibitors also have immunomodulatory effects that promote antitumour immune responses.

    • Giulia Petroni
    • , Silvia C. Formenti
    • , Selina Chen-Kiang
    •  & Lorenzo Galluzzi
  • Review Article |

    In the short time since SARS-CoV-2 infections emerged in humans, much has been learned about the immunological processes that underlie the clinical manifestation of COVID-19. Here, the authors provide an overview of the pathophysiology of SARS-CoV-2 infection and discuss potential therapeutic approaches.

    • Matthew Zirui Tay
    • , Chek Meng Poh
    • , Laurent Rénia
    • , Paul A. MacAry
    •  & Lisa F. P. Ng
  • Review Article |

    The RNA-sensing retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are important inducers of type I interferons and other antiviral immune mediators. Here, Jan Rehwinkel and Michaela Gack explain how members of the RLR family are regulated and reflect on the importance of the RLRs in viral infection, autoimmunity and cancer.

    • Jan Rehwinkel
    •  & Michaela U. Gack
  • Review Article |

    Here a group of leaders in the field define our current understanding of ‘trained immunity’, which refers to the memory-type responses that occur in the innate immune system. The authors discuss our current understanding of the key epigenetic and metabolic processes involved in trained immunity and consider its relevance in immune-mediated diseases and cancer.

    • Mihai G. Netea
    • , Jorge Domínguez-Andrés
    • , Luis B. Barreiro
    • , Triantafyllos Chavakis
    • , Maziar Divangahi
    • , Elaine Fuchs
    • , Leo A. B. Joosten
    • , Jos W. M. van der Meer
    • , Musa M. Mhlanga
    • , Willem J. M. Mulder
    • , Niels P. Riksen
    • , Andreas Schlitzer
    • , Joachim L. Schultze
    • , Christine Stabell Benn
    • , Joseph C. Sun
    • , Ramnik J. Xavier
    •  & Eicke Latz
  • Review Article |

    Innate lymphoid cell (ILC) subsets with defined phenotypes can adapt to local environmental cues through transdifferentiation. Studies of such plasticity have improved our understanding of the biological roles of ILCs and offer promise for new strategies to treat inflammatory diseases and cancer.

    • Suzanne M. Bal
    • , Korneliusz Golebski
    •  & Hergen Spits
  • Review Article |

    Recent single-cell studies have revealed a previously unappreciated heterogeneity among endothelial cells that line the lymphatic sinuses of the lymph nodes. In this Review, the authors describe these various lymphatic endothelial cell types and how they support the trafficking of cells and antigens through lymph nodes.

    • Sirpa Jalkanen
    •  & Marko Salmi
  • Review Article |

    Recently, antibody-mediated control of HIV infection has received considerable attention. Here, the authors discuss the importance of CD8+ T cells in HIV infection and suggest that efforts to develop vaccines that target these cells in conjunction with B cells should be renewed.

    • David R. Collins
    • , Gaurav D. Gaiha
    •  & Bruce D. Walker
  • Review Article |

    Immune subversion by primary tumours plays a key role in metastatic spread. This Review explores how primary tumours interfere with the crosstalk between immune cells to promote a chronic inflammatory yet immunosuppressed state that enables immune evasion and the formation of metastases.

    • Hannah Garner
    •  & Karin E. de Visser
  • Review Article |

    In this Review, the authors encourage us to extend our concept of memory by considering the diverse cell types within a barrier tissue. They propose that any long-term resident or essential tissue cell type can store memory of previous immune events and cooperate in memory recall.

    • Jose Ordovas-Montanes
    • , Semir Beyaz
    • , Seth Rakoff-Nahoum
    •  & Alex K. Shalek
  • Review Article |

    This Review considers how IgA operates alongside IgM, IgG and IgD to provide immune protection and promote homeostasis at mucosal tissue sites. The authors highlight how some of these neglected mucosal antibody isotypes may strengthen the communication between the mucosal and systemic immune compartments.

    • Kang Chen
    • , Giuliana Magri
    • , Emilie K. Grasset
    •  & Andrea Cerutti
  • Review Article |

    This Review describes the breakdown of ‘mucosal firewalls’ in patients with inflammatory bowel disease, involving immunological pathways that regulate microbial recognition and killing, immune responses to microorganisms and the reinforcement of the intestinal barrier.

    • Roberta Caruso
    • , Bernard C. Lo
    •  & Gabriel Núñez
  • Review Article |

    Getting medicines to the right place at the right time is key to their success. Nanomedicines — drugs formulated in carrier materials that are smaller than 100 nm — show promise in enhancing tumour immunotherapy, owing to the ability to focus their action on target tissues and control their immunomodulatory properties, as reviewed here.

    • Darrell J. Irvine
    •  & Eric L. Dane
  • Review Article |

    This Review discusses the various ways in which B cells, plasma cells and antibodies shape the immune response in cancer. B cells can have both protumour and antitumour roles, and the authors discuss the potential of targeting these cells for therapy.

    • George V. Sharonov
    • , Ekaterina O. Serebrovskaya
    • , Diana V. Yuzhakova
    • , Olga V. Britanova
    •  & Dmitriy M. Chudakov
  • Progress |

    Freeman and colleagues draw our attention to the existence of different forms of PDL1 — cell bound and various extracellular forms. Recent studies show that PDL1 on exosomes can inhibit antitumour immune responses and may be a useful biomarker for the management of cancer immunotherapy.

    • Dhouha Daassi
    • , Kathleen M. Mahoney
    •  & Gordon J. Freeman