Reviews & Analysis

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.

The duration of immunity to coronavirus disease 2019 (COVID-19) from prior infection and longer-term risk of reinfection are currently unclear. Cromer and colleagues discuss the immune control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the implications of this for the future control of the pandemic.

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.

Here, the authors propose that SARS-CoV-2 induces a prothrombotic state, with dysregulated immunothrombosis in lung microvessels and endothelial injury, which drive the clinical manifestations of severe COVID-19. They discuss potential antithrombotic and immunomodulating drugs that are being considered in the treatment of patients with COVID-19.

In this Perspective, Cobey, Larremore, Grad and Lipsitch argue that dose-sparing regimens of COVID-19 vaccines can reduce disease incidence, prevalence and burden and explain why they think that such strategies would also slow the rate of viral escape from vaccine or naturally induced immunity.

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.

A timeline of the major scientific discoveries during the first year of the COVID-19 pandemic showcases the collaborative efforts that enabled the key aspects of the immune response to SARS-CoV-2 to be reported at unprecedented speed.

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.

Intestinal IgA is important for regulating the commensal microbiota and for preventing harmful pathogens from colonizing the intestine. In this Review, Huus, Petersen and Finlay consider the host, bacterial and environmental factors that shape IgA–microbiota interactions in the intestine.

Although many healthy newborns carry preleukaemic clones, only a small minority of infants will develop overt B cell acute lymphoblastic leukaemia. Here, the authors explore the idea that infections can serve as immune stressors that drive the progression of B cell acute lymphoblastic leukaemia.

Ras homology (RHO) GTPases are signalling proteins that have crucial roles in triggering multiple immune functions. Here, the authors describe the recent discovery of new RHO GTPase partners and genetic mutations in RHO GTPase signalling hubs that may provide novel therapeutic opportunities.