Abstract 2223: Membranous expression of programmed cell death-ligand 1 (PDL1) on cancer cells is induced by cisplatin in an ATR dependent manner

Cancer cells frequently develop strategies allowing to escape potential immune attacks by the host. One central component of this defense mechanism is the PDL1-PD1 axis with PDL1 expression on the surface of antigen presenting cells. DNA damaging chemotherapeutic are known to have suppressive effect on the immune system. Possible effects on immune checkpoints, however, are poorly understood. We investigated if Cisplatin, a widely used chemotherapeutic for treatment of ovarian and lung carcinomas, might influence expression of PDL1 on cancer cells of these pathologies. Treatment of cell lines as well as precision-cut tissue slices from patient tumors with clinically relevant dosages of cisplatin led to a significant induction of PDL1 protein in cancer cells as revealed by Western Blot and IHC analyses. This effect was independent on ATR or ATM activity since pre-treatment with ATR or ATM inhibitors had no significant effect on cisplatin induced total PDL1 protein levels. Interestingly, however, we observed an almost complete inhibition of cisplatin-induced membranous PDL1 upon ATR but not ATM inhibition as revealed by FACS analysis in unfixed cells. The role of the ATR axis was further corroborated by the finding that presentation of PDL1 at the cell surface was paralleled by phosphorylation of CHK1. Together our data indicate an important role of DNA damage induced ATR/CHK1 activity on the localization of PDL1 at the surface of cancer cells. These data implicate that combination of cisplatin with either anti-PD1 or anti-PDL1 antibodies or ATR/CHK1 inhibitors should reduce immunosuppressive mechanisms and enhance chemotherapy efficacy. Citation Format: Lea Schaaf, Meng Dong, Simon Heine, Heiko van der Kuip, Walter E. Aulitzky. Membranous expression of programmed cell death-ligand 1 (PDL1) on cancer cells is induced by cisplatin in an ATR dependent manner. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2223.