A recent study by Ascic et al. demonstrates that in situ reprogramming of tumor cells into conventional dendritic cell (cDC)-like cells using viral-PIB transcription factors creates an immunogenic tumor microenvironment with T cell recruitment and activation. The study highlights the potential of tumor-specific cancer immunotherapy using in vivo reprogrammed cDCs.

Following on from the discovery that innate immune pathways are shared widely across the tree of life comes another surprise: Hobbs et al. show that viruses targeting animals and bacteria also use highly conserved tools to fight back. Why such mechanisms remain seemingly unchanged despite the rapid coevolution among hosts and pathogens is now a key open question for the field.

Combinations of the highly polymorphic KIR and HLA-I genes are associated with numerous human diseases. Interpreting these associations requires a molecular understanding of the multiple killer-cell immunoglobulin-like receptor (KIR)–human leukocyte antigen-1 (HLA-I) receptor–ligand interactions on natural killer (NK) cells and identifying the salient features that underlie disease risk. We hypothesize that a critical discriminating factor in KIR–HLA-I interactions is the selective detection of HLA-I-bound peptides by KIRs. We propose a ‘peptide selectivity model’, where high-avidity KIR–HLA-I interactions reflect low selectivity for peptides conferring consistent NK cell inhibition across different tissue immunopeptidomes. Conversely, lower-avidity interactions (including those with activating KIRs) are more dependent on HLA-I-bound peptide sequence, requiring an appreciation of how HLA-I immunopeptidomes influence KIR binding and regulate NK cell function. Relevant to understanding N

Tissue-resident memory (TRM) T cells not only control infection and cancer, but also contribute to inflammatory disease. In a recent study, Obers et al. demonstrate that retinoic acid (RA) and TGF-β direct TRM residency in mice, with RA uniquely retaining cells in the intestine by limiting migration. This discovery highlights the potential for harnessing local residency cues to enhance tissue-specific TRM responses.

Solute carrier proteins (SLCs) are pivotal for maintaining cellular homeostasis by transporting small molecules across cellular membranes. Recent discoveries have uncovered their involvement in modulating innate immunity, particularly within the cytosol. We review emerging evidence that links SLC transporters to cytosolic innate immune recognition and highlight their role in regulating inflammation. We explore how SLC transporters influence the activation of endosomal Toll-like receptors, cytosolic NODs, and STING sensors. Understanding the contribution of SLCs to innate immune recognition provides insight into their fundamental biological functions and opens new avenues to develop possible therapeutic interventions for autoimmune and inflammatory diseases. This review aims to discuss current knowledge and identify key gaps in this rapidly evolving field.

Effector-triggered immunity (ETI) enables hosts to react to pathogens by monitoring few key cellular processes. ETI responses are assumed to be similar toward related pathogen effectors. However, recent evidence from the invertebrate model Caenorhabditis elegans and pore-forming toxins indicates a much more complex and specific ETI than previously anticipated.