Review Articles

The vasculature that forms in tumours and supports tumour growth is abnormal and limits T cell entry into tumours. Here, the authors review how the tumour vasculature acts as a barrier to effective antitumour immunity and the therapeutic strategies to overcome this.

In this Review the authors explain how different routes of exposure to food antigens can contribute to the development of food allergies. They discuss how allergic sensitization occurs against food antigens and focus on how IgE and mast cells ultimately drive the allergic pathology.

During pregnancy, innate immune mechanisms at the maternal–fetal interface are important for protecting the developing fetus from pathogens. However, excessive immune activation can be harmful to the fetus, and these pathways must be properly regulated. Here, the authors discuss the growing understanding of the unique innate immune pathways that operate in the maternal and fetal compartments of the placenta.

Iron is crucial for cellular metabolism, but its availability varies greatly within and between individuals and populations. This Review highlights how iron regulates innate and adaptive cellular and humoral responses affecting protection against infections, tumours and autoimmunity.

T cells have an essential role in immune responses to Mycobacterium tuberculosis, but the mechanisms by which they may provide protective immunity remain poorly understood. This Review explores the knowns and unknowns of T cell immunity in tuberculosis and how recent technologies may inform the design of T cell-targeted TB vaccines.

Macrophages are crucial regulators of fibrosis. Here the authors describe how distinct subsets of monocytes and macrophages cooperate with fibroblasts across tissues to control progression from inflammation to fibrosis.

Pattern recognition receptors (PRRs) are typically associated with innate immune activation, but there is an emerging subset of inhibitory pattern recognition receptors (iPRRs) that limit cell activation. This Review from Meyaard and colleagues highlights our growing understanding of iPRR biology, focusing on leukocyte-associated immunoglobulin-like receptor (LAIR1).

In vivo chimeric antigen receptor (CAR) engineering has emerged as a promising off-the-shelf therapeutic approach for hard-to-treat diseases such as solid tumours, offering key advantages such as streamlined production, the elimination of patient-specific manufacturing, reduced costs and simplified logistics. In this Review, Yang and colleagues provide an overview of current in vivo CAR engineering strategies, highlighting existing challenges and discussing future directions for the field.

Cytotoxic T lymphocytes and natural killer cells destroy target cells using a mechanically active cytolytic immune synapse. This Review examines the various ways in which mechanical forces contribute to the potency, specificity and overall efficacy of the cytotoxic response.

In this Review, Male and Jones provide an overview of the current vaccines that are offered during pregnancy and to newborns, explaining the rationale behind the different vaccination programmes and the unique challenges that come with immunizing these populations.

In this Review, Tse-Kang, Wani and Pukkila-Worley discuss how nematodes, such as Caenorhabditis elegans, rely on ‘patterns of pathogenesis’ as opposed to the sensing of specific ligands by pattern-recognition receptors to activate innate immune responses. They explain why this approach to immune surveillance is beneficial to C. elegans and consider how studies in C. elegans can inform our understanding of mammalian immunity.

In this Review, Kato and Kita discuss the complex interactions between airway epithelial cells and immune cells that contribute to the development of asthma and chronic rhinosinusitis. They highlight recent advances in understanding the clinical heterogeneity of these diseases and explain the progress that has been made in developing new therapies.

Beyond exhaustion, CD8⁺ T cells can adopt various dysfunctional states, including tolerant, anergic, senescent, ignorant and dying states, that compromise their ability to eradicate viruses or tumours. Here, the authors describe how these states may be distinguished, how they arise and the implications for immunotherapy.

Regulatory T (T_reg) cells have an important role in the maintenance of immune tolerance and continuously circulate in the body. During this migration, they engage in bidirectional crosstalk with lymphatic and blood endothelial cells, which regulates vascular permeability and determines T_reg cell migration patterns and tissue residency. This Review examines the molecular mechanism of these interactions and how they could be targeted in the context of autoimmunity, transplantation and cancer.

In this Review, the authors explain how post-translational protein modification by the small ubiquitin-like modifier (SUMO) family is emerging as an important regulator of immune cell function. Notably, inhibition of sumoylation is showing promise as a cancer therapy and may also have therapeutic use in various autoimmune conditions.

B cells are major drivers of systemic immunity, but they also act locally in non-lymphoid organs. This Review highlights new insights into mechanisms of tissue B cell function as well as efforts to leverage this biology for immunotherapy.

Besides its beneficial effects against infection, trained immunity has recently been implicated in inflammation-related disorders and is being exploited in cancer immunotherapy. These advances may enable the development of therapeutic interventions to modulate trained immunity towards promoting human health.

Kidney diseases affect millions globally. Advances in understanding immunological mechanisms and disease endotypes have enhanced diagnostic accuracy and treatment strategies. Here, the authors review our current understanding of immune mechanisms of kidney disease and highlight the interplay between renal and systemic immunity.

Recent studies suggest that biomolecular condensates — membrane-less assemblies of proteins and nucleic acids — are involved in regulating gene expression to ensure proper immune cell development. This Review highlights how condensate formation enhances the precision and flexibility of gene regulatory networks that guide fate during both normal and pathological immune cell development.

This Review summarizes mechanisms for the regulation of cGAS–STING signalling, describes its crosstalk with other signalling pathways, and outlines the diverse cellular outcomes of cGAS–STING biology and its roles in inflammatory disease, ageing and tumorigenesis.