Chemotherapy elevates cell surface PD-L1 and MHC-I expression in apoptotic gastric cancer cells

Background: The programmed cell death-ligand 1 (PD-L1) combined positive score is used as a patient selection tool and predictive factor for anti-programmed cell death-1 (PD-1)/PD-L1 therapy in gastric Cancer. However, the expression of PD-L1 and major histocompatibility complex class I (MHC-I) can be affected by conventional treatment approaches.

Objective: In this study, we examined the effects of chemotherapy on surface PD-L1 and surface MHC-I expression in living and apoptotic gastric Cancer cells. AGS (moderately differentiated) and SNU-1 (poorly differentiated) cells were treated 5-Fluorouracil (5-Fu), cisplatin, mitomycin c (MMC), and FOLFOX (5-Fu, leucovorin, and oxaliplatin).

Methods: To quantify the expression levels of surface PD-L1 or surface MHC-I on living and apoptotic cells, the cells were co-stained with annexin V and PD-L1 or MHC-I antibodies. The percentages of single positive (annexin V-negative, PD-L1-positive; annexin V-negative, MHC-I-positive) and double positive (annexin V-positive, PD-L1-positive; annexin V-positive, MHC-I-positive) cells were analyzed by flow cytometry.

Results: Every tested chemotherapeutic agent increased the levels of surface PD-L1 and surface MHC-I, although the extents of increase differed in AGS and SNU-1 cells. In AGS cells, 5-Fu caused the largest increases in surface PD-L1 and surface MHC-I. However, 5-Fu caused the weakest increases in surface PD-L1 and surface MHC-I in SNU-1 cells. Notably, chemotherapy-mediated increases in surface PD-L1 and surface MHC-I mostly occurred on apoptotic cells.

Conclusion: Our findings reveal that chemotherapy mainly increases surface PD-L1 and surface MHC-I on apoptotic gastric Cancer cells.

MHC-I; PD-L1; apoptosis; gastric cancer.