人白细胞介素-15与18协同增强肿瘤浸润淋巴细胞体内对结肠癌细胞的杀伤功能

目的 观察白细胞介素(IL)-15与IL-18体内增强肿瘤浸润淋巴细胞(TIL)杀伤功能的效果.方法 用IL-15与IL-18共同刺激从结肠癌患者分离得到的TIL,通过测定其分泌转化生长因子(TGF)-β、IL-4、干扰素(IFN)-γ水平以及TIL的杀伤活性.用IL-15与IL-18共同刺激的TIL与结肠癌细胞SW480共孵育后,接种到SCID鼠皮下,测定肿瘤生长的大小、肝脏转移的肿瘤结节多少、血清中IL-4、IFN-γ水平以及腹腔巨噬细胞的吞噬能力.结果 IL-15与IL-18共同作用于TIL,能够抑制TGF-β、IL-4的分泌(P＜0.05),促进IFN-γ的分泌(P＜0.05).IL-15与IL-18共同作用于TIL后,能明显提高TIL对结肠癌细胞SW480的杀伤活性(P＜0.05).肝脏转移的肿瘤结节明显减少,血清中IFN-γ水平明显升高,腹腔巨噬细胞的吞噬能力增强.结论 IL-15与IL-18协同刺激体内能增强TIL对结肠癌细胞的杀伤功能.

Synergic effects of human interleukin-15 and-18 on cytotoxic function of tumor-infiltrating lymphocytes in vivo

Objective To explore the synergic effects of interleukin (IL)-15 and IL-18 con cytotoxic function of tumor-infiltrating lymphocytes (TIL). Methods IL-15 and IL-18 co-stimulated TIL from patients with colon cancer and the function of TIL was evaluated by detecting transforming growth factor (TGF)-β, IL-4, interferon (IFN)-γ and cytotoxicity of TIL. IL-15 and IL-18 co-stimulated TIL from the patients with colon cancer, then SW480 cells were incubated with TIL and subcutaneously inoculated into SCID mice. The function of TIL was tested by detecting tumor size on SCID mice, tumor metastasis of liver, IL-4 and IFN-γ in serum and the phagocytic power of the mouse peritoneal macrophages. Results Synergetic effects of IL-15 and IL-18 could inhibit the secretion of TGF-β and IL-4 from TIL (P < 0.05), increase the secretion of T IFN-γ from TIL ( P < 0.05) , meanwhile could enhance the cytotoxicity of TIL. TIL under synergetic effects of IL-15 and IL-18 could extend survival time and inhibit tumor growth significantly (P < 0.05). TIL also could inhibit the tumor metastasis of liver. In addition, TIL could enhance the phagocytic power of the mouse peritoneal macrophages and increase the expression of IFN-γ and decrease the IL-4 expression. Conclusion IL-15 and IL-18 can synergeticaly enhance cytotoxic function of TIL on human colon cancer.