Induction of cytotoxicity of human tumor-infiltrating lymphocytes against autologous tumor cells and its application for cancer therapy

1)用白细胞介素2（IL-2）诱导自体外周血淋巴细胞（PBL）培养的淋巴因子激活的杀伤（LAK）细胞过继免疫治疗恶性肿瘤。经动脉或腔内局部注射LAK细胞的治疗效果上级全身静脉注射。2）实体癌肿瘤浸润细胞中半数为T淋巴细胞，CD 8 ^+T淋巴细胞的比例高于外周血淋巴细胞。结直肠癌肿瘤浸润淋巴细胞（TIL）中含有γ δ T细胞，且以CD 8 ^+ T细胞为主。3）单纯IL-2培养的TIL不足以进行体外扩增，我们发现，通过加入20%的LAK细胞诱导产生的条件培养基，TIL在培养物中有效地扩增。新鲜分离的TIL对肿瘤细胞无细胞毒作用，培养过程中TIL的细胞毒作用逐渐增强，2 ~ 3周达高峰，4 ~ 7周消失。植物血凝素（PHA）可部分恢复培养的TIL细胞毒性。5）术前瘤内注射生物反应调节剂OK-432激活进展期胃癌的TIL，并与对照组患者进行比较。尽管缺乏TIL的患者的生存率没有差异，但TIL的活化可提高中等或以上程度TIL患者的3年生存率。

1) Cancer patients were treated with the adoptive immunotherapy with lymphokine-activated killer (LAK) cells which were induced by culture of autologous peripheral blood lymphocytes (PBL) with interleukin-2(IL-2). Local administration by intraarterial or intracavital infusions of LAK cells produced a superior therapeutic efficacy to systemic administration by intravenous infusions.2)A half of tumor-infiltrating cells into human solid cancers consisted of T lymphocytes and the proportion of CD8^+T lymphocytes were greater than that of PBL.Tumor-infiltrating lymphocytes (TIL) contained gammadelta T cells and the majority of those cells in colorectal cancers were CD8^+ gammadelta T cells whose lineage was different from that of PBL.Hepatocellular carcinoma contained a greater number of gammadelta TIL than other human solid cancers.3)Culture of TIL with IL-2 alone was inadequate for their in vitro expansion, and we found that TIL effectively expanded in culture by addition of 20% conditioned medium derived from LAK cell induction.4)Cytotoxicity against tumor cells was notdetected in freshly isolated TIL.Cytotoxicity of TIL gradually increased in culture, reached its maximum at 2 to 3 weeks, and disappeared at 4 to 7 weeks. Phytohemagglutinin (PHA) was found to be capable of partial restoration of the diminished cytotoxicity of cultured TIL.5) TIL of advanced gastric cancer were activated in vivo by preoperative intratumoral injection with a biological response modifier, OK-432, and survival of patients after curative sugery was compared with control patients. Although there was no difference in survival of patients with scanty TIL,the activation of TIL improved 3-year survival in patients with TIL of a medium or over degree.