Low dose irradiation increases adoptive cytotoxic T lymphocyte migration in gastric cancer

Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic; however, the inefficient migration of adoptive immune cells to tumors is one of the rate-limiting factors of ACI. The present study investigated whether 2 Gy low dose irradiation (LDI) was able to increase the migration of adoptive lymphocytes to gastric cancer cells. Treatment with 2 Gy LDI resulted in marked chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 production from gastric cancer cell lines. A Transwell chamber migration assay demonstrated enhanced transmigration of cytotoxic T lymphocytes to gastric cancer cells following LDI treatment. After 2 Gy LDI application to established gastric carcinoma in nude mice, labeled immune cells were infused by intravenous injection and concentrated fluorescence signals were observed at the tumor sites within the mice, with a peak signal at 8-h LDI. Increased numbers of adoptive T cells at the tumor sites were also observed using flow cytometry. Furthermore, a case study of a patient with metastatic gastric cancer who had received ACI treatment combined with 2 Gy LDI provided further evidence that 2 Gy LDI is able to recruit antitumor effector T cells to tumor sites. Therefore, the ability of 2 Gy LDI to convert tumors into inflamed peripheral tissues may be exploited to overcome obstacles at the effector phase of the antitumor immune response and improve the therapeutic efficacy of immunotherapy.