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Here the authors identify and characterize the development and function of an IFN-γ-producing CD8αβ+ subset of γδ T cells that contributes to malignancy.
CAR T cells have shown great promise in treating some cancers and are now being applied to other diseases. Here the authors engineer mouse and human T cells and show that a single infusion can result in lasting remission from asthma in mice.
Cancer and aging are associated with each other, but underlying mechanisms contributing to this correlation are unclear. Here the authors identify a dysfunctional T cell state that is distinct from typical T cell exhaustion and only occurs in the tumor microenvironment during later life.
Singh and colleagues show Tigit controls the generation of germinal center-derived plasma cell precursors that give rise to long-lived differentiated progeny in the bone marrow.
Here the authors show that sepsis and its resolution alter cancer susceptibility by epigenetically altering resident macrophages resulting in retention of T cells that increase antitumoral immunity.
In this study, the authors suggest that in the lung ApoE is a checkpoint for monocyte-to-macrophage differentiation triggered by the dectin1–Card9 pathway.
Here the authors show that a heteropolysaccharide from a commensal bacteria commonly found in the Korean food kimchi is able to bolster antitumor immune responses by instructing tumor-associated macrophages to release lipocalin-2, which sequesters iron away from tumor cells contributing to the immune response to attack these cells.
Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8+ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.
Koh et al. show that loci active in differentiated effector T cells are poised in early T precursors before the expression of T cell antigen receptors in a manner dependent on the chromatin remodeling complex mammalian SWItch/Sucrose Non-Fermentable and the PU.1–RUNX1 and BCL11B–RUNX1 complexes.
Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.
Cupedo and colleagues show that neutrophils promote a tumor-supportive microenvironment via a self-amplifying interaction between neutrophils and bone marrow stromal cells. This scenario creates a promyeloma niche that is difficult to treat despite targeted therapies directed at the myeloma cells.
Here the authors identify the transcription factor MEF2C as essential for human NK cell function and viral immunity in mice and humans. This control is exerted via regulation of lipid metabolism, and deficiency in MEF2C can be overcome by oleic acid supplementation.
CD103+ T cells are associated with control over tumors but how this is mediated is unclear. Here the authors show that CD61 colocalizes and functionally combines with CD103 in the T cell synaptic response to promote antitumor T cell responses.
Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.
The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8+ T cells with positive response to anti-PD-1 therapy.
Here the authors present a method they call CM-Drug for the identification of combination drugs that can boost the efficacy of immune checkpoint blockade therapy. They validate this method with melanoma and lung cancer models in mice and explore in further depth one hit from their screen, the thyrotropin-releasing hormone (TRH) analog taltirelin.
Abraham and colleagues found that antigen-triggered degranulation in IgE-sensitized mast cells was mediated by the inflammasome components NLRP3 and ASC.
Here the authors use three different mouse models to show that prior infection or mRNA vaccination can protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) independently of antibodies, highlighting the importance of T cell-derived interferon-γ (IFN-γ) in host defense and the need to consider this measure of protection in vaccination.
Zhang and colleagues found that Omicron RBD binding to Siglec-9 impaired phagocytosis and antigen presentation in macrophages, an effect abrogated by an F375S mutation in the spike protein of Omicron.