Interleukin-18 and -12 synergistically enhance cytotoxic functions of tumor-infiltrating lymphocytes.
- Author:
Zhi-Fen CHEN
1
;
Rui ZHOU
;
Bing XIA
;
Chang-Sheng DENG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Animals; CD8-Positive T-Lymphocytes; immunology; metabolism; Cell Line, Tumor; Female; Humans; In Vitro Techniques; Interferon-gamma; metabolism; Interleukin-10; metabolism; Interleukin-12; pharmacology; Interleukin-18; pharmacology; Interleukin-4; metabolism; Lymphocytes, Tumor-Infiltrating; drug effects; immunology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Stomach Neoplasms; immunology; Tumor Necrosis Factor-alpha; metabolism; Xenograft Model Antitumor Assays
- From: Chinese Medical Journal 2012;125(23):4245-4248
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDThe 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.
METHODSTILs 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.
RESULTSIL-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).
CONCLUSIONIL-18 and IL-12 can synergistically enhance cytotoxic functions of TILs from human gastric cancer.
