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IL-23 promotes tumor growth in preclinical cancer models and correlates with adverse clinical outcomes. Here, Becher and colleagues find that IL-23 produced by tumor-associated macrophages stabilizes Treg cell identity, promoting immunosuppression and tumor growth.
Here, the authors target intratumoral Treg cells to enhance antitumor immunity without affecting systemic Treg cell function and identify JMJD1C as a critical epigenetic regulator of tumor Treg cell fitness.
Here, the authors characterize two distinct Treg cell populations in the visceral adipose tissue of lean and high-fat diet-fed mice. ST2+ Treg cells are dominant in male mice and are transcriptionally driven by GATA3 and PPARγ, regulators that limit the differentiation of the more female-dominant population of CXCR3+ Treg cells that are T-bet dependent. Functional distinctions are also evident in glucose tolerance and adipose inflammation.
Reis e Sousa et al. show that cDC2As and cDC2Bs are derived from distinct subsets of bone marrow pre-cDC2s, suggesting that the two lineages are ontogenetically determined.
Here, the authors enhance their nasally delivered chimpanzee adenoviral-vectored SARS-CoV-2 vaccine with an Omicron-matched vaccine (ChAd-SARS-CoV-2-BA.5-S) that stimulates mucosal immunity in mice and hamsters and shows cross-reactive CD8+ memory T cell-driven protection against antigenically distant strains.
Siliciano and colleagues describe the generation of bispecific antibodies that target the HIV-1 envelope protein (Env) on the surface of HIV-1-infected cells and the receptor CD16 on the surface of NK cells to induce the NK cell-mediated lysis of HIV-1-infected cells and reduce the viral reservoir.
Here the authors show that lithium carbonate can revitalize tumor-reactive CD8+T cells by shunting cytosolic lactic acid into the mitochondria for oxidation, indicating that lithium ions might be applied as a cancer immunotherapy.
Xue and colleagues show that the transcription cofactor Tle3 cooperates with Runx3, Tcf1 and Tbet to limit a central memory and promote an effector memory cell signature in CD8+ T cells.
Divangahi and colleagues identify a mechanism of heterologous immunity by BCG involving cross-talk between conventional memory T cells and innate memory cells against influenza A virus infection’.
Callahan et al. show that GC and extra-GC sites spawn distinct MBC subsets. MBC precursors have open chromatin regions (OCRs) that will remain open in MBC progeny, with extra-GC and GC-derived MBCs having distinct OCRs and functions.
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.