Sensitization of Epidermal Growth Factor Receptor (EGFR) Inhibitors Induced by Radiotherapy Combined with Programmed Death Ligand-1 (PD-L1) Inhibitors

Abstract

To explore the effect of radiotherapy combined with programmed death ligand-1 (PD-L1) inhibitors on the sensitization of epidermal growth factor receptor (EGFR) inhibitors, 76 patients with nonsmall cell lung cancer (NSCLC) were rolled into group A (lung adenocarcinoma, 55 cases) and group B (lung squamous carcinoma, 21 cases). Another 63 healthy volunteers were set as controls (group C). Patients in group A were rolled into mutation group (15 cases) and wild group (22 cases) regarding the presence of EGFR mutations. The sPD-L1 protein in serum samples was determined via enzyme-linked immunosorbent assay (ELISA). Expressions of PD-L1, EGFR, and immune interferon (IFN-γ) in lung cancer cell lines (LCCL) mutant PC9 and HCC827, and wild-type A549 and H1299 were analyzed. After separation of T lymphocytes, four LCCLs and T lymphocytes were co-cultured to detect the proliferation and apoptosis of T lymphocytes. The results showed that PD-L1 level in EGFR-sensitive mutant LCCLs PC9 and HCC827 after X-ray irradiation was obviously inferior to controls (P < 0.05). The proliferation of T cells in mutant LCCLs PC9 and HCC827 was substantially superior to co-culture system (co-CS) (P < 0.05). After the PC9 co-CS was treated with X-rays, PD-L1 inhibitors, and X-rays combined with PD-L1 inhibitors, the secretion of IFN-γ was markedly increased versus controls (P < 0.05). In short, radiotherapy combined with PD-L1 inhibitors can enhance the proliferation of T cells and inhibit their apoptosis, and greatly increase the secretion of IFN-γ by T cells.