Review Articles in 2021

Vignali and colleagues discuss the pleiotropic roles of interferon-γ (IFNγ) in the tumour microenvironment; on the one hand, it acts as a ‘teammate’ to promote antitumour immune responses and, on the other hand, it acts as an ‘opponent’ promoting tumour growth and suppressing immune responses.

The transcription factor TCF1 is essential for early T cell development, and recent advances have uncovered context-dependent functions in mature T cells. This review summarizes key findings on TCF1 across the field of T cell immunity and explores their translational potential.

This Review covers the role of natural killer cells in acute and chronic viral infections, with emphasis on human infections and insights from patients with primary immunodeficiencies affecting natural killer cells. It also describes the emerging data on how natural killer cells are involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

In this Review, Maria Mittelbrunn and colleagues highlight the involvement of T cells in diseases associated with ageing. In particular, the authors discuss how T cells contribute to inflammageing and the potential of targeting these populations for therapy of age-related diseases.

In this Review, Iannacone and Guidotti discuss the immunobiology and pathogenesis of hepatitis B virus (HBV) infection, with a particular focus on the role of CD8⁺ T cells, and examine recent breakthroughs that challenge current dogmas.

This Review discusses our current understanding of the pathophysiological mechanisms of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome associated with chimeric antigen receptor (CAR) T cell therapies, and how this might be used for the prevention or management of these toxicities.

This Review discusses evidence from clinical studies and animal models regarding the effects of the gut microbiota on modulating immune responses to vaccination as well as the immunological mechanisms that potentially mediate these effects.

This Review examines the metabolic adaptations that occur in CD8⁺ T cells in the settings of infection and cancer. The authors discuss the key metabolic features of activated, memory, tissue-resident and dysfunctional CD8⁺ T cell populations and also consider how overall host metabolism can affect the CD8⁺ T cell response.

Here, Harald Prüss discusses how autoantibodies can contribute to neurological diseases. The identification of specific autoantibodies to neuronal and glial targets has increased our understanding of autoimmunity in the central nervous system and led to the reclassification of some diseases previously thought to result from infection or ‘idiopathic’ causes.

Immunotherapeutic approaches to cancer can be affected by metabolic restrictions that limit the potency of anticancer T cell responses. In this Review, DePeaux and Delgoffe discuss the metabolic features of the tumour microenvironment that limit anticancer immune responses, as well as emerging therapeutic approaches to target these.

Fibroblasts are not just crucial structural cells; they exist as multiple functionally diverse populations, defined by their location and context, and regulate tissue immunity. Here, the authors review the immunological properties of fibroblasts, comprising both pro-inflammatory and immunosuppressive activities, in different tissues and disease states.

Mark Schmitt and Florian Greten describe the mechanisms by which chronic inflammation can initiate tumorigenesis and by which tumour-elicited and therapy-induced inflammation can promote colorectal cancer, as well as the role of extrinsic factors such as diet, the microbiota and the mycobiota.

Successful adoptive cell therapy for cancer depends on the expansion and persistence of tumour-specific T cells with stem-like memory or precursor characteristics. Here, the authors describe approaches to generate these cells by in vitro culture methods, by modulating transcriptional, metabolic and/or epigenetic programming, and by fine-tuning antigen receptor signalling.

Peter Taylor and colleagues provide an overview of the neutralizing monoclonal antibody therapies that have been developed to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discuss the clinical utility of these antibodies.

This Review from Jeff Rathmell and colleagues serves as a guide to immunologists on how to select the appropriate tools and techniques to interrogate metabolism in their experimental systems. The authors provide advice for avoiding common mistakes and on how best to employ metabolomics.

In this review, Cezmi Akdis discusses how epithelial barrier-damaging agents linked to industrialization, urbanization and modern life may explain the increased prevalence of allergic disease as well as a wide range of autoimmune and metabolic conditions in which immune responses to translocated bacteria have systemic effects.

The cGAS–STING pathway drives innate immune activation in response to cytosolic DNA. This is important for immunity to bacteria and viruses, but aberrant cGAS–STING activity is also linked to inflammatory disease. Here, Ablasser and colleagues discuss how cGAS–STING signalling contributes to various autoimmune, inflammatory and degenerative diseases and describe the novel therapeutics targeting this pathway.

Regulatory T cells present in non-lymphoid tissues such as the skin, fat and muscle are distinct from their counterparts in lymphoid tissues. Their functions extend beyond immune surveillance to the control of local metabolism, tissue repair and tissue cell progenitors, as discussed in this Review.

In this Review, Kipnis and colleagues explain how signals from the immune system can shape host behavioural responses, even in the absence of infection or disease. In particular, the authors focus on the cytokine pathways that modulate behavioural responses and consider the evolutionary basis of these neuroimmune interactions.

In this Review, Deborah Fowell and Minsoo Kim highlight the complexity of the biochemical and mechanical cues that facilitate T cell migration. They explain how effector T cells are able to use these cues to navigate through complex tissue environments to respond to pathogens and other immunological challenges.