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The G396R coding variant in IGHG1, which encodes membrane-bound IgG1 heavy chain, might have arisen within the Southeast Asian population as a potential evolutionary event on an archaic haplotype background. This variant potentiates immune resilience against various life-threatening organisms, illustrating the interplay of human evolution and immune adaptation.
We integrated single-cell RNA-sequencing data to provide comprehensive profiles of the cellular composition of the tumor microenvironment and identify their underlying genetic determinants across 23 cancer types. We used this resource to delineate the biological mechanisms by which genetic variants shape the cellular composition of the tumor microenvironment.
PD-1 is a critical modulator of CD8+ T cell activation and exhaustion. Sen and colleagues show that a cell-state-specific enhancer tunes PD-1 expression exclusively in exhaustion and that deletion of this enhancer improves CD8+ T cell function.
When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months
Liu and colleagues show that a previously described G396R variant of the human IGHG1 gene offers increased protection from SARS-CoV-2 and bacterial infections.
Effector CD8+ T cells with cytotoxic ability are crucial for immunotherapy success. Two studies show that salt (NaCl) supplementation can enhance the effector function of CD8+ T cells and boost their antitumor responses.
Immunocytokines are cytokine-based fusion proteins with therapeutic potential. New CD45-targeted immunocytokines can reprogram systemic anti-tumor immunity by prolonged retention on T cells and dendritic cells while minimizing systemic toxicities through intratumoral delivery.
This Comment discusses the explosion in innovative systems biology approaches in infectious disease studies. We outline the numerous challenges associated with these technologies from standardizing data science approaches to reproducibility of findings, as well as cost.
Tumor cells in emerging cancers modify their gene expression to avoid immune control, a process known as immunoediting. We found that genome-wide gene expression changes in breast tumors after oncogene induction in genetically engineered mice were dominated by the epigenetic repression of innate and adaptive immune genes. Immunoevasion by tumors was reversed by a DNA methyltransferase inhibitor.
Mucosal vaccine boosters are expected to enhance protection against SARS-CoV-2 infection. A study now reveals that the delivery device — through either intranasal sprayers or nebulizers — also influences the mucosal immunity and protection efficacy in non-human primates.
Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.
Here the authors pull apart the cellular composition of the tumor microenvironment using RNA sequencing data from a wide variety of cancer types. They identify immunity quantitative trait loci and integrate these data with analysis of colorectal cancer cohorts, creating a polygenic risk score and a database for community access.