Strategies that interfere with the binding of the receptor programmed cell death protein-1 (PD-1) to programmed death ligand-1 (PD-L1) have shown marked efficacy against many advanced cancers, including those that are negative for PD-L1. Precisely why patients with PD-L1 negative tumors respond to PD-1/PD-L1 checkpoint inhibition remains unclear. Here, we show that platelet-derived PD-L1 regulates the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promotes T cell-induced cancer cytotoxicity. These results suggest that the successful outcomes of PD-L1 based therapies in patients with PD-L1 negative tumors may be explained, in part, by the presence of intra-tumoral platelets. Altogether, our findings demonstrate the impact of non-cancer/non-immune cell sources of PD-L1 in the tumor microenvironment in the promotion of cancer cell immune evasion. Our study also provides a compelling rationale for future testing of PD-L1 checkpoint inhibitor therapies in combination with antiplatelet agents, in patients with PD-L1 negative tumors.

The coronavirus pandemic has taken a detrimental toll on the lives of individuals globally. In addition to the direct effect (e.g., being infected with the virus), this pandemic has negatively ravaged many industries, particularly food retail, food services, and hospitality. Given the novelty of the disease, the true impact of COVID-19 remains to be determined. Because of the nature of their work, and the characteristics of the workers, individuals in the food retail, food service, and hospitality industries are a group whose vulnerability is at its most fragile state during this pandemic. Through this qualitative study, we explored workers' perspectives on the impact of COVID-19 on their mental health and coping, including screening for post-traumatic stress disorder (PTSD) and alcohol use disorder symptoms. Twenty-seven individual interviews were conducted, audio-recorded, transcribed, and analyzed using qualitative content analysis. Four key themes emerged: being infected and infecting others, the unknown, isolation, and work and customer demands. Considering the many uncertainties of COVID-19, workers in these three industries were experiencing heightened levels of mental distress because of where they worked and the already existing disparities they faced on a daily basis before the pandemic started. Yet they remained hopeful for a better future. More studies are needed to fully understand the magnitude, short-term, and long-term effects of COVID-19. Based on this study's findings, programs are critically needed to promote positive coping behaviors among at-risk and distressed workers. Recommendations for employers, occupational health and safety professionals, and policy stakeholders to further support these service workers are discussed.

The invasive trophoblast cells of the equine placenta migrate into the endometrium to form endometrial cups, dense accumulations of trophoblast cells that produce equine chorionic gonadotropin between days 40 and 120 of normal pregnancy. The mechanisms by which the trophoblast cells invade the endometrium while evading maternal immune destruction are poorly defined. A gene expression microarray analysis performed on placental tissues obtained at day 34 of gestation revealed a >900-fold upregulation of mRNA encoding the cytokine IL-22 in chorionic girdle relative to noninvasive chorion. Quantitative RT-PCR assays were used to verify high expression of IL-22 in chorionic girdle. Additional quantitative RT-PCR analysis showed a striking increase in IL-22 mRNA expression in chorionic girdle from days 32 to 35 and an absence of IL-22 expression in other conceptus tissues. Bio-informatic analysis and cDNA sequencing confirmed the predicted length of horse IL-22, which carries a 39 extension absent in IL-22 genes of humans and mice, but present in the cow and pig. Our discovery of IL-22 in the chorionic girdle is a novel finding, as this cytokine has been previously reported in immune cells only. IL-22 has immunoregulatory functions, with primary action on epithelial cells. mRNA of IL-22R1 was detected in pregnant endometrium at levels similar to other equine epithelia. Based upon these findings, we hypothesize that IL-22 cytokine produced by the chorionic girdle binds IL-22R1 on endometrium, serving as a mechanism of fetal-maternal communication by modulating endometrial responses to trophoblast invasion.

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breaches are alarming; they also point to an urgent need to the convergence of technology, legislation, user policies, and awareness in protecting privacy.