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In this Resource paper, the authors integrate T cell antigen receptor, B cell antigen receptor and exome sequencing comparing early and metastatic breast cancer in humans, showing how the immune response and tumors coevolve.
Jakubzick and colleagues show that interstitial macrophages across various tissues display similar coordinated chemokine signatures in humans and mice.
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.
Here the authors show how the liver affects the immune response to pancreatic ductal adenocarcinoma and that cancer immunity and survival outcomes after surgery might be bolstered by therapeutic intervention on hepatocyte release of serum amyloid A proteins.
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.
In this Resource, the authors integrate multiomics data to show the effect of the transcription factors Blimp-1 and c-Maf on IL-10 and type 1 and 17 responses, which together protect against pathobiont-induced colitis.
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.
Kratchmarov et al. identified a GATA3+ TH2 population that expresses the transcription factors TCF1 and LEF1 and sustains type 2 inflammation in tissues over a human lifetime, despite chronic antigen exposure.
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.
In this Resource article, the authors integrate genomic, bioinformatic and flow cytometric data from human bone marrow to provide an atlas of hematopoietic progenitor cell states in health and disease.
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.