PD-L2 of tumor-derived exosomes mediates the immune escape of cancer cells via the impaired T cell function

The function and regulation of PD-1/PD-L1 axis have been widely studied for immune escape of various cancer cells. However, the underlying function and regulation of PD-L2 remain poorly to be understood. We demonstrate that PD-L2 is majorly secreted and expressed on exosomes with surface localization by tumor cell. In order to investigate the function of TDE-PD-L2 in the regulation of lymphocytes, we explored the expression profiles of TDE-PD-L2 on lymphocytes of PBMC using RNA-seq. Overall design: To investigate the function of tumor cell-derived exosome PD-L2 (TDE-PD-L2) in the regulation of lymphocytes of PBMC, we established 786-O cell lines in which PDCD1LG2 gene has been knockout by CRISPR-Cas9. Exosomes isolated from 786-O CTR and PD-L2 KO culture supernatants of equal numbers of cells were feeded to PMA and ionomycin stimulated lymphocytes isolated from peripheral blood lymphocytes in 10cm Petri dish for 72h.