The expression of PDCD1 and CD274 in T cells and macrophages correlated positively with COVID-19 severity (preprint)

The immune responses underlying the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To help understand the pathology of coronavirus disease 2019 (COVID-19) pandemics, public data were analyzed and the expression of PDCD1 (encoding PD-1) and CD274 (encoding PD-L1) in T cells and macrophages were identified to correlate positively with COVID-19 severity.

Single-cell transcriptome analysis of the immunosuppressive effect of differential expression of tumor PD-L1 on responding TCR-T cells (preprint)

PD-L1 expression levels in tumors do not consistently predict cancer patients’ response to PD-(L)1 inhibitors. We therefore evaluated how tumor PD-L1 levels affect the anti-PD-(L)1 efficacy and T cell function. We used MART-1-specific TCR-T cells (TCR-T MART-1 ) stimulated with MART-1 27-35 peptide-loaded MEL-526 tumor cells with different proportions of them expressing PD-L1 to perform cellular assays and high-throughput single-cell RNA sequencing. Compared to control T cells, TCR-T MART-1 were more sensitive to exhaustion and secreted lower pro-inflammatory but higher anti-inflammatory cytokines with increasing proportions of PD-L1 + tumor cells. The colocalization of T cells and tumor cells in gene clusters correlated negatively with the proportion of PD-L1 + tumor cells and positively with immune cell cytotoxicity. Moreover, elevated proportion of PD-L1 + tumor cells increased PD-L1 expression and decreased PD-1 expression on T cells and enhanced T cell death. The expression of PD-1 and PD-L1 in T cells and macrophages also correlated positively with COVID-19 severity.