Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.23.217059v1?rss=1 Authors: Ding, R., Liu, S., Wang, S., Chen, H., Wang, F., Xu, Q., Zhu, L., Dong, X., Gu, Y., Chao, C.-C., Gao, Q. Abstract: 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-TMART-1) stimulated with MART-127-35 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-TMART-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. Copy rights belong to original authors. Visit the link for more info