title: Interleukin-18 and -12 synergistically enhance cytotoxic functions of tumor-infiltrating lymphocytes.
abstract: 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-7901 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)1 (tumor necrosis factor (TNF)-α, interferon (IFN)-γ) 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-α and IFN-γ ((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).
  
  
  CONCLUSIONS
  IL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human gastric cancer.
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Zhi-Fen
authors.initials: ZF
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Chang-Sheng
authors.initials: CS
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma