Reviews & Analysis

This Review outlines the mechanisms by which the microbiota alters the efficacy and immunotoxicity of established and emerging cancer treatments, and discusses the benefits and limitations of microbiota-targeting interventions that are being investigated to improve patient outcomes.

Epidemiological studies and mouse models suggest that stress can affect the evolution, dissemination and outcome of malignancies. In this Review, Ma and Kroemer present insights into the complex neuro-immune interactions that link stress to cancer, with a focus on stress-associated immunomodulatory molecules, and discuss their implications for cancer therapy.

In this Perspective, the authors consider the distinct contributions made by T helper 2 cells and group 2 innate lymphoid cells during the course of a helminth infection. Although anti-helminth drugs are effective, reinfection is common and there are currently no available vaccines — a better understanding of T helper 2 cell and group 2 innate lymphoid cell interplay could lead to new anti-helminth strategies.

Epidemiological evidence indicates that physical exercise can lower cancer incidence and mortality. This Perspective discusses the importance of muscular activity for maintaining a healthy immune system and the potential mechanisms by which exercise affects anticancer immunity.

Personalized neoantigen vaccines offer the potential to boost immune response a patient against their specific cancer antigens. Here, Katsikis, Ishii and Schliehe discuss the challenges that currently limit this therapeutic approach, including those related to neoantigen selection and adjuvants, and post-vaccine challenges such as the immunosuppressive tumour microenvironment. Moreover, they consider solutions that could help to overcome these obstacles.

The MHC class I-related protein 1 (MR1) presents specific small molecule antigens to MR1-restricted T (MR1T) lymphocytes. These cells play an important role in infection and cancer, and strategies to target these cells are of considerable therapeutic interest. In this Review, McWilliam and Villadangos provide a comprehensive description of the antigen presentation pathway of MR1, which is fundamental for the understanding of MR1-mediated immunity and the potential therapeutic manipulation of MR1T cells.

The protective effect of vaccines is often poorest in low-income countries. Here, the authors explore the immunological factors that may explain the geographical variation in vaccine responsiveness and the ways in which they might be modulated to ensure effective vaccination in regions where it is needed most.

The families of tetraspanins and galectins are essential for the organization of molecules on the surface of lymphocytes, and deficiencies in specific family members can lead to impaired immunity, tumour development and autoimmunity. This Review investigates the molecular mechanisms of membrane organization by tetraspanins and galectins, specifically their role in B cell and T cell proliferation, survival and migration, as well as in antibody production and T cell polarization, and discusses potential therapeutic opportunities.

This Review discusses how the study of novel mouse models of human ADAR1 deficiency has led to the identification of the innate immune receptors recognizing endogenous immunostimulatory double-stranded RNA and their respective downstream signalling pathways that induce autoinflammatory pathology.

This Review covers the biology of anti-cytokine autoantibodies and their varied roles in causing, preventing and treating diseases. Recent reports of anti-type I interferon autoantibodies in critical COVID-19 have led to renewed interest in this topic, which offers fascinating insights into the reversibility of immune tolerance and the origins of autoimmunity in otherwise healthy individuals.

Cryptosporidium are protozoan parasites that infect intestinal epithelial cells and can cause severe diarrhoeal disease, particularly in malnourished children. This Review summarizes the immune mechanisms that protect against this parasitic infection, highlighting the innate mechanisms that detect Cryptosporidium at the intestinal epithelium and the adaptive immune mechanisms that mediate resistance.

This Review provides a guide to complement and its emerging roles in processes beyond innate immune defence such as in early development, tissue immunometabolism, tissue regeneration and cancer immunity. Moreover, our improved understanding of its role in disease pathology has opened new options for complement-based therapeutics.

Phagocytosis-mediated cell death — also known as ‘phagoptosis’ — regulates developmental processes, cell turnover and immunity to infections and cancer. Here, Brown summarizes the key molecular interactions involved in cell death by phagocytosis and the relevance of this process for host health.

Recent studies have revealed a family of antigen-presenting cells (APCs) marked by the transcription factor RORγt that fundamentally shape immunity, inflammation and tolerance. This article reviews heterogeneity among RORγt⁺ APCs, their associated functions and the future promise of this new field.

This Review summarizes how the processes of thymic selection together ensure that the T cell repertoire is fully functional and safe. In the thymus, T cell receptor signal strength is integrated with distinct stromal cues to result in positive or negative selection of thymocytes or the generation of regulatory cells.

Microglia are increasingly implicated in the maintenance and regeneration of myelin, which is damaged with normal ageing and in several neurodegenerative diseases. This article reviews the mechanisms by which microglia support and restore myelin health and the factors that influence these crucial microglial functions.

SARS-CoV-2 infection can lead to a diverse array of chronic symptoms, collectively termed ‘long COVID’. In this Review, Altmann and colleagues explore current thinking about the pathophysiology of long COVID and discuss potential immunological mechanisms.

This Review describes recent advances in the field of 3D in vitro modelling technologies that enable a better understanding of immune cell and tumour cell interactions in the tumour microenvironment. The authors explain how such systems can be used to assess the efficacy of novel immunotherapies, including personalized immunotherapies, for patients with cancer.

Memory B cells are critical for protection against repeated infections, particularly with viral variants, and understanding their function and development is key for successful vaccine development. This Review discusses the cellular and molecular mechanisms of memory B cell generation and reactivation and how these processes shape antibody diversity and breadth.

This article reviews growing evidence suggesting that narcolepsy, a chronic sleep disorder caused by deficiency of hypocretin (also known as orexin), has an immune-mediated basis, explores the potential role of autoreactive lymphocytes in the disease process, and proposes future research directions to elucidate its pathogenesis.