Tumor cell-intrinsic PD-L1 promotes tumor-initiating cell generation and functions in melanoma and ovarian cancer.

ABSTRACT: As tumor PD-L1 provides signals to anti-tumor PD-1⁺ T cells that blunt their functions, αPD-1 and αPD-L1 antibodies have been developed as anti-cancer immunotherapies based on interrupting this signaling axis. However, tumor cell-intrinsic PD-L1 signals also regulate immune-independent tumor cell proliferation and mTOR signals, among other important effects. Tumor initiating cells (TIC) generate carcinomas, resist treatments and promote relapse. We show here that in murine B16 melanoma and ID8agg ovarian carcinoma cells, TIC express more PD-L1 versus non-TIC. Silencing PD-L1 in B16 and ID8agg cells by shRNA ("PD-L1^lo") reduced TIC numbers, the canonical TIC genes nanog and pou5f1 (oct4), and functions as assessed by tumorosphere development, immune-depen

SUBMITTER: Gupta HB 

PROVIDER: S-EPMC5547561 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature