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For decades, beta-blockers have been used widely to treat cardiovascular diseases. Surprisingly, new data show how these inhibitors can also improve immunotherapy against tumors and chronic infections.
Kupffer cells, hepatic resident macrophages, are the first line of defense against liver metastases by engulfing disseminated malignant cells. We found that ERMAP expressed on tumor cells binds to galectin-9 and dectin-2 on Kupffer cells to deliver pro-phagocytosis ‘eat me’ signals to Kupffer cells to restrict liver metastases.
Yuan and colleagues show that ERMAP expression on cancer cells delivers an ‘eat me’ signal to Kupffer cells by binding to Gal-9–dectin-2 on Kupffer cells and triggering phagocytosis.
The malate shuttle is understood to control the NAD+/NADH balance. Here the authors show that GOT1, a central enzyme in the malate shuttle, rather promotes antiviral CD8+ T cell responses by detoxifying ammonia.
Peduto and colleagues report a role for ADAM12+ mesenchymal stromal cells at the tumor margins and their interaction with immune cells to promote a permissive ‘protumor’ environment.
Current acellular pertussis vaccines prevent disease but do not prevent nasal infection and transmission of Bordetella pertussis. However, immunology is helping to design new vaccines that induce sterilizing immunity.
The first conference on ‘Infection and Immunity’ was organized by the Institute for Basic Science and Korean Association of Immunologists and held in Daejeon, South Korea, from 12 to 14 July 2023. The conference focused on the biology of CD8+ T cells in the context of viral disease and cancer.
On 20–23 June 2023, the 10th International γδ T cell conference was held in Lisbon, Portugal, bringing together basic, translational and clinical researchers studying γδ T cells in health and disease.
The APOE4 allele is a major genetic risk factor for the development of late-onset Alzheimer’s disease (AD). In this manuscript, Butovsky and colleagues suggest that APOE4 impairs the microglial response in AD by inducing TGFβ-mediated checkpoints.
Here the authors use single cell profiling of T cells across the human lifespan to show that a suboptimal TCR shift in T cells as we enter older age results in a molecular signature that resembles that of T cells from newborns and children.
After vaccination, spike-specific CD8+ T cells play an important part in the immediate immune response to breakthrough SARS-CoV-2 infection, whereas the B cell and neutralizing antibody responses come into effect 2 weeks after infection.
That regulatory T cells can change their phenotypes has been shown in mouse models of atherosclerosis and other autoimmune diseases. We suspected that this phenomenon would also be true in humans. To test this hypothesis, we developed a strategy to identify human ‘exTreg’ cells and found that they express a cytotoxic transcriptome.
Satija and colleagues use multimodal sequencing technologies and cross-modality integration tools to define distinct subpopulations of CD8+ T cells that are predictive of COVID-19 severity.
Wherry and colleagues define the kinetics of vaccine-primed recall immune responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection, highlighting rapid activation of memory T cells and broadly enhanced immune responses in previously vaccinated individuals.
The mechanisms by which noncoding genetic variation shapes tissue macrophage phenotypic diversity remain obscure. Glass and colleagues define cell-intrinsic and environmental effects contributing to genetic control of Kupffer cell transcription.
We show that multivalent epitope display on the surface of viral-sized particles functions as a ‘stand-alone’ danger signal by evading inhibitory pathways to trigger a unique mode of B cell receptor signaling. The activation, survival and proliferation of B cells stimulated with particulate antigen is highly enhanced compared with those stimulated with soluble antigen, and does not require co-stimulation from T cells.
Many transcription factors contain intrinsically disordered regions whose functions are not well characterized. An intrinsically disordered region in TCF-1 has now been found to have an essential function in coordinating T cell lineage commitment.