IL-2激活的TIL对自体肿瘤细胞的杀伤活性及其与LAK细胞活性的比较

THE CYTOTOXICITY TO AUTOLOGOUS TUMOR CELLS OF TUMOR-INFILTRATING LYMPHOCYTE (TIL) ACTIVATED BY IL-2 AND ITS COMPARISON WITH THE CYTOTOXICITY OF LAK CELLS

肿瘤浸润性淋巴细胞(TIL)经白细胞介素2(IL-2)体外培养后具有很强的体内外抗肿瘤作用,且有一定的靶细胞特异性,其抗肿瘤效果强于淋巴因子激活的杀伤细胞即LAK细胞(P<0.01)。从瘤体中新鲜分离到的TIL对自体肿瘤细胞的杀伤活性极低,经IL-2体外培养后,其杀伤活性逐渐增高,以培养至7～25d的杀伤活性最强,这与IL-2使TIL分泌3种抗癌淋巴因子包括IL-2、IFN-γ、淋巴毒素(LT)增加有关。体外培养25d后,TIL的抗肿瘤活性下降,实验表明这与培养过程中TIL的Lyt-2^+细胞(Tc)减少而L3T4^+细胞(T_H)增多有关。TIL经冻存复苏和IL-2体外培养后仍保持很强的抗肿瘤活性,冻存前后比较未见显著差异(P>0.05),这为间断地运用TIL治疗复发性、晚期肿瘤提供了一条可行的途径。

We have shown that tumor-infiltrating lymphocyte (TIL) cultured in interleukin-2 (IL-2) acquired a potent antitumor activity and had target cell specificity.TIL exhibited higher cytotoxicity to autologous tumor cells than that of LAK cells grown under identical conditions (P<0.01).TIL isolated freshly from tumor mass had very low cytotoxicity to autologous tumor cells.After culture in IL-2, the cytotoxicity of TIL increased,, and was at highest level between 7~25 d and then declined.The increase of antitumor activity of TIL may'be related to the increased capability of secreting IL-2, IFN-Y and LT by culture in IL-2.The decrease of antitumor activity of TIL may be related to the(changes'in the phenotype of TIL, in which Lyt-2+ cells decreased but LsT4+ cells increased to be the majority in the later stage of culture.We have also shown that TIL had almost the same antitumor activity even after thaw from cryopre-servation (P>0.05), so that it is possible to treat recurrent and unresectable tumor using TIL periodically.