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Tumor cells exploit G-protein-coupled receptor (GPCR) signaling networks to promote angiogenesis, grow and metastasize. We show that tumor cells leverage a GPCR–Gαs–protein kinase A (PKA) signaling axis to polarize CD8+ T cells into a dysfunctional state, thereby limiting the tumor infiltration and cytotoxic function of these cells and reducing the efficacy of current immunotherapies.
Despite the absence of MHC class II molecules on tumor cells, stem-cell-like CD4+ T cells specific for tumor neoantigens can mediate profound antitumor effects by licensing antigen-presenting cells and augmenting antitumor CD8+ T cells in the tumor microenvironment and draining lymph nodes.
Confusion exists as to whether transitional dendritic cells are a bone fide subset or just a transitional state, as the name indicates. New data are complicating matters further by showing some interesting heterogeneity in these cells.
CD8+ virtual memory T cells have been studied mainly for their antimicrobial functions but it seems that their descendants can contribute to inflammation and hair loss in the context of alopecia areata.
Nimmerjahn and colleagues review posttranslational modification of immunoglobulins and how these posttranslational modifications influence antibody effector function. Furthermore, they discuss the implications of immunoglobulin posttranslational modifications when designing therapeutic antibodies for various clinical indications.
Naive B cells activated during infection enter the germinal center (GC) reaction, in which high-affinity antibodies are generated. A new study has uncovered a distinct metabolic requirement for B cells poised to undergo the GC reaction, whose activation required lactate dehydrogenase A-dependent aerobic glycolysis.
Buggert and colleagues provide a broad picture in this review of circulating and tissue-resident memory CD8+ T cells, which are ultimately responsible for effective immune surveillance.
We identified an abundant macrophage population with a distinct transcriptomic signature in the murine mammary gland and milk during lactation. These macrophages are monocyte-derived, depend on colony-stimulating factor (CSF-1) and reside adjacent to alveoli. Human milk also contains macrophages comprising three subsets with a partial resemblance to the murine counterparts.
COVID-19 vaccines have been successful, but their duration and level of protection could be improved to cover all SARS-CoV-2 variants. A self-assembling enveloped virus-like particle vaccine combining features of mRNA and protein vaccines might provide a way forward.
Single-cell RNA sequencing distinguishes subsets of fibroblastic reticular cells and predicts pathways that support immune function via crosstalk with lymphocytes.
Extravasation of blood into the brain and activation of innate immune cells are hallmarks and therapeutic targets in neurological diseases. We show that specific blood proteins induce distinct receptor-mediated gene programs in microglia and that the blood coagulation protein fibrin has a causal role in pathogenic innate immunity in models of neurological diseases.
Presentation of signal peptides by HLA-E to natural killer cells prevents cell lysis via interactions with the inhibitory CD94–NKG2A receptor. A study now reveals an unexpected level of sophistication and heterogeneity in this receptor–ligand interaction.
Devant and Kagan review the biochemical and cell biological mechanisms that control gasdermin D pore-forming activity and its diverse downstream immunological effects.
First Nations peoples of Australia have disproportionate rates of chronic comorbidities such as diabetes and renal disease. A study of COVID vaccination in First Nations peoples reveals that perturbed antibody responses can occur in individuals with comorbidities in a way strongly associated with altered IgG glycosylation patterns.
Indigenous populations are disproportionately affected by COVID-19, but are rarely studied. An investigation of the immune response of Australian First Nations people to SARS-CoV-2 vaccination and infection shows a major effect of comorbidities.
The magnitude and quality of the germinal center response after vaccination decline with age. We found that T follicular helper (TFH) cells are enriched in the dark zone of germinal centers in aged mice, which impairs the expansion of the follicular dendritic cell network upon immunization and reduces antibody responses.
In mice and humans, changes in neutrophil phenotypes and functionality during aging aggravate thromboinflammation in ischemic brain injury and determine the pathology associated with strokes. In mice, inhibition of CXCL3 signaling and rejuvenation of bone marrow offer ways of restricting brain injury and improving stroke outcomes.
In this Review, Künzli and Masopust provide updates on our understanding of the biology of memory CD4+ T cells as well as key technological advances that facilitate their characterization.
