摘要
Background The role of tumor-infiltrating lymphocytes （TILs） in the immunopathogenesis of individual cancer is not clear and is a challenge for anti-tumor immunotherapy. This study aimed to investigate the effects of interleukin （IL）-18 and -12 on cytotoxic functions of TILs, Methods TILs from postoperative gastric cancer patients were costimulated with IL-18 and IL-12. SGC-7g01 tumor cells were pre-incubated with TILs and subcutaneously injected into BALB/C SCID mice. The function of TILs was evaluated by measuring tumor sizes in tumor-bearing mice, T helper （Th）l （tumor necrosis factor （TNF）-a, interferon （IFN）-y） and Th2 cytokine levels （IL-10 and IL-4） in serum and cytotoxicity of mouse natural killer （NK） and CD8＋ T cells. Results IL-18 and IL-12 synergistically inhibited the growth of SGC-7901 cells in vivo and significantly extended the survival rate of SGC-7901-bearing mice （66.7% vs. 13.7%, P 〈0.01）. Moreover, TILs could promote the secretion of TNF-a and IFN-y （（130.34±7.65） vs. （210.63±12.31） pg/ml, P 〈0.01; （14.23±1.97） vs. （30.52±2.12） pg/ml, P 〈0.01）, and downregulate IL-10 and IL-4 secretion （（103.72±11.21）vs. （61.36±5.41） pg/ml, P=0.021; （49.36±4.67）vs. （28.48±3.86） pg/ml, P=0.024）. Conclusion IL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human gastric cancer.
Background The role of tumor-infiltrating lymphocytes （TILs） in the immunopathogenesis of individual cancer is not clear and is a challenge for anti-tumor immunotherapy. This study aimed to investigate the effects of interleukin （IL）-18 and -12 on cytotoxic functions of TILs, Methods TILs from postoperative gastric cancer patients were costimulated with IL-18 and IL-12. SGC-7g01 tumor cells were pre-incubated with TILs and subcutaneously injected into BALB/C SCID mice. The function of TILs was evaluated by measuring tumor sizes in tumor-bearing mice, T helper （Th）l （tumor necrosis factor （TNF）-a, interferon （IFN）-y） and Th2 cytokine levels （IL-10 and IL-4） in serum and cytotoxicity of mouse natural killer （NK） and CD8＋ T cells. Results IL-18 and IL-12 synergistically inhibited the growth of SGC-7901 cells in vivo and significantly extended the survival rate of SGC-7901-bearing mice （66.7% vs. 13.7%, P 〈0.01）. Moreover, TILs could promote the secretion of TNF-a and IFN-y （（130.34±7.65） vs. （210.63±12.31） pg/ml, P 〈0.01; （14.23±1.97） vs. （30.52±2.12） pg/ml, P 〈0.01）, and downregulate IL-10 and IL-4 secretion （（103.72±11.21）vs. （61.36±5.41） pg/ml, P=0.021; （49.36±4.67）vs. （28.48±3.86） pg/ml, P=0.024）. Conclusion IL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human gastric cancer.
