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Here the authors show that immune cell exclusion and immunosuppression in the melanoma microenviromment are driven by nerve growth factor interactions with tropomyosin receptor kinase A on melanoma cells and that a tropomyosin receptor kinase inhibitor can sensitize these tumors to immune checkpoint blockade.
Chevrier and colleagues uncovered a hierarchical cytokine circuit arising from the pairwise effects of TNF with IL-18, IFN-γ or IL-1β, which explains the organism-wide response of the host to bacterial sepsis.
Ravichandran et al. performed a systems immunology study to profile the responses to pneumococcal vaccines in older adults. They identified distinct baseline features that could capture responses to Prevnar and Pneumovax and sex-biased differences in Prevnar responses.
Gao and colleagues report a structure-guided chimeric antigen based on the A35 and M1 antigens of the mpox virus (MPXV) that induces strong MPXV-specific antibody responses and protection against lethal doses of vaccinia virus in mice.
Ikaros, Helios and Aiolos are transcription factors involved in lymphocyte development. Here the authors dissect the regulatory role of these Ikaros family members to understand their contribution to NK cell development and functions.
Carnosine is a mobile buffering metabolite. Here the authors link carnosine accumulation, hypoxia and intracellular pH homeostasis in cancer cells as a mechanism of tumor immune evasion via NFX1 degradation and galectin-9 activity.
Terminally differentiated plasma cells reside in multiple tissues to contribute to local immunity. Nutt and colleagues examined tissue-specific differences in long-lived plasma cell lifespan and function, identifying unique transcriptional attributes in addition to the core plasma cell program.
Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.
Löhning and colleagues identify an alternative promoter for the Il1rl1 gene that drives IL-33 receptor expression in cytotoxic T cells and T-helper 1 cells
TCF1+ ‘stem-like’ CD4+ T cells have a capacity for self-renewal and effector differentiation when required. Here the authors show how these stem-like T cells mediate allograft rejection via the replenishment of their effector differentiation.
Wang and colleagues revealed how oleic acid produced by thymic epithelial cells could affect the developing thymocytes to differentiate into peripheral regulatory T cells.
Colonna and colleagues show that the transcription factor Aiolos controls chromatin accessibility and histone acetylation at genes linked to the activation of intestinal intraepithelial lymphocytes.
Cyster and colleagues show that CD97–CD55 interactions, which trigger Gα13–ARHGEF–Rho cytoskeletal signaling, are needed for proper MZ B cell positioning/retention in the spleen and for optimal antibody responses to T cell-independent antigens.
Pulendran and colleagues delineated the mechanisms underlying the nonspecific antiviral effects exerted by the BCG vaccine against SARS-CoV-2 and reveal a pivotal role for BCG-specific CD4+ T cells that produce interferon-γ in imprinting a persistent antiviral innate program in the lung, mediating heterologous viral protection.
Here, the authors show that combining γ9δ2 TCR-mediated metabolic and co-stimulatory stress targeting by chimeric NKG2D or anti-CD277 co-receptors shapes transcriptomic heterogeneity of engineered T cells and is associated with improved control of solid tumors.
Induced pluripotent stem cell (iPSC)-derived macrophages (iMACs) are being used to make chimeric antigen receptor (CAR) macrophages for immunotherapy. Here the authors design a second-generation macrophage-specific CAR by integrating CD3ζ and toll/IL-1R (TIR) domains resulting in an M1-polarized CAR-iMAC with increased antitumor functions.
Wu and colleagues identify gene networks and transcription factors that control the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.
Mandal and colleagues report how the chromatin modulator BRWD1 mediates extensive changes in 3D chromatin topology during B cell development by converting static to dynamic cohesin.
Iwawura et al. identify a noncanonical role for NOD1, independent from its CARD-mediated proteoglycan sensing. Interactions between NOD1 and STAT5 are required for optimal lymphopoiesis in response to homeostatic cytokines.
Love and colleagues find an inhibitory function for CD3ζ ITAMs in response to low-affinity ligands, meaning that CD3ζ can perform a dual function in TCR signaling by playing a positive or negative role depending on the affinity of the TCR for its peptide ligand.