Review Articles

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.

In this Review, the authors discuss recent advances, current challenges and future prospects in exploiting both vertebrate and invertebrate immune systems for the control of flaviviral and alphaviral diseases.

Short-chain fatty acids (SCFAs) are microbial metabolites that regulate mucosal barrier integrity and immune cell functions. This Review summarizes latest insights into how SCFA levels might determine inflammatory and allergic disease outcomes by controlling the crosstalk between diet, the microbiome and immunity.

Haematological malignancies are associated with inflammation in the bone marrow. In this Review, the authors discuss how tumour-associated inflammation affects the normal functions of the bone marrow and supports the outgrowth and survival of malignant cells. Moreover, they describe how the inflammatory changes in the bone marrow differ in myeloid and lymphoid malignancies.

This Review explains how cytokines contribute to the pathogenesis of inflammatory bowel disease (IBD). The author highlights the cytokine-targeting drugs that are already being successfully used in the clinic and discusses the potential of other cytokine-modulating drugs in IBD.

Acute infection and other insults cause extensive remodelling in the bone marrow to drive the production of new blood cells, often prioritizing the production of mature myeloid cells at the expense of other blood cell types. Here, the authors describe how haematopoiesis is affected by acute demand and how this can contribute to inflammatory disease and cancer when dysregulated.

Immune responses to pathogens and self-antigens show sex-based differences, with female individuals generally more susceptible to autoimmunity and male individuals more vulnerable to infections. In this Review, the authors explore the role of hormones and genetics in shaping immune responses, and discuss genetic and epigenetic contributions to altered X-linked gene expression that affect immune responses.

In this Review, the authors discuss the origins of regulatory T (T_reg) cells in the periphery and the mechanisms by which T_reg cells are induced, as well as the regulation of the suppressive function of these cells. Moreover, they examine evidence for and  mechanisms of T_reg cell dysfunction in common autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis.

This Review highlights new insights into the biology of inflammasomes from the perspective of structural and mechanistic studies, revealing how the supramolecular complexes that activate inflammatory caspases are assembled and regulated, to induce cytokine maturation and release, as well as pyroptotic cell death.

The first immune-targeted drug for type 1 diabetes (T1D), teplizumab, received regulatory approval by the US FDA in 2022. In this Review, Herold, Walker and colleagues examine the immune mechanisms that underpin T1D and provide an overview of immune-targeted strategies for T1D that are currently in development.

Immune cell engagers — antibody-based molecules engineered to direct immune effector cells to recognize and kill cancer cells — represent a rapidly expanding approach in cancer therapy. Here, the authors bring us up to date with the targets, challenges and opportunities for harnessing the anticancer activities of T cells, natural killer cells and myeloid cells with immune cell engagers.

This Review provides an updated assessment of the expanding family of T cell-activating bacterial superantigens, emphasizing potential roles of these toxins in various disease states as well as their contribution to the evolution of the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes.

This Review from Wolfgang Kastenmüller and colleagues highlights the heterogeneity that exists among lymph nodes at different anatomical locations. The authors consider the factors that contribute to lymph node heterogeneity and explain the relevance of this for the immune response, particularly in the contexts of vaccination and cancer.

This Review from Wellford and Moseman considers the unique immunology of the olfactory mucosa. The authors describe how stromal cells, innate immune cells and adaptive immune cells cooperate to defend the olfactory mucosa, protecting the host from potentially serious respiratory or neurotropic infections. They also discuss the relevance of olfactory mucosal immunology for the fields of vaccination and neurodegeneration.

The induction of antigen-specific immune tolerance is considered the 'holy grail' of disease management for autoimmunity and organ transplantation. Are we getting any closer to this goal? Here, the authors update us on the current progress and challenges to the therapeutic induction of antigen-specific immune tolerance.

In this Review, Butterfield and Najjar discuss the rationale for combination strategies in cancer, including combinations of different immunotherapies and combinations of immunotherapies with other types of therapies. Moreover, they examine the evolution of biomarker approaches to guide such therapies.

In this Review, Liston et al. discuss the biology of regulatory T cells (T_reg cells) in the brain. They consider how T_reg cells are recruited to the brain and their anti-inflammatory and reparative functions in brain tissue. Finally, they highlight the potential for targeting brain T_reg cells to treat a range of neurological diseases.

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.

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.