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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.
Investigation of neutrophil heterogeneity in tumours reveals the irreversible programming of long-lived, pro-angiogenic neutrophils that drive tumour progression.
In this Progress article, Fooksman and colleagues review recent advances in the study of long-lived plasma cells, using genetic labelling tools, RNA sequencing and in vivo imaging to characterize the differentiation and survival of this rare cell type in mice and humans.
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.
A preprint by Kim et al. shows that the brain parenchyma can be seeded with age with clonal haematopoiesis-derived monocytes that drive neuropathology.
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.
While anticipating the development of a COVID-19-specific vaccine, several randomized controlled trials (RCTs) explored the potential of BCG vaccination to protect against COVID-19, based on trials demonstrating beneficial effects of BCG vaccination on unrelated infections and all-cause mortality in neonates in high-mortality geographical settings. Results are now available from 12 RCTs, which suggest that BCG vaccination is not an effective intervention against COVID-19. That the BCG–COVID-19 trials failed to meet expectation emphasizes the importance of rigorous clinical trials to validate hypotheses, even in urgent situations such as a pandemic.
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.
A preprint by Kwok et al. describes the identification of common neojunction-derived antigens that could serve as targets for ‘off the shelf’ vaccines or adoptive cell therapies for patients with various types of cancer.
The failure of T cell-targeted vaccines for HIV in clinical trials is likely due to impaired degranulation of low-avidity CD8+ T cells in the context of low levels of antigen presentation.
In this Comment article, the authors alert us to recent studies of ancient DNA that advance our understanding of the origins of autoimmune disease, providing evidence that our disease risk has been shaped by pathogen-driven evolution.
