Mise K, Kan N, Okino T, Nakanishi M, Satoh K, Teramura Y, Yamasaki S, Ohgaki K, Tobe T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Cancer Res. 1990 Oct 1;50(19):6199-202.
We examined the effects of heat treatment on tumor cells and antitumor effector cells in order to investigate the combined effects of hyperthermia and immunotherapy including adoptive immunotherapy. Plasmacytoma MOPC104E syngeneic to BALB/c mice was used as the tumor cell line, while fresh spleen cells immunized to MOPC104E (IM-FSC) and interleukin-2-cultured lymphocytes induced in vitro from IM-FSC (CL) were used as the effector cells. Tumor cells or effector cells were heat-treated in a water bath at 42 degrees C for 30 or 60 min. Tumor cells heat-treated at 42 degrees C for 30 min grew temporarily and then regressed in the tumor transfer test, whereas untreated tumor cells showed no regression under any conditions. Furthermore, fresh spleen cells of mice inoculated with heat-treated tumor cells from regressed tumors showed marked tumor-neutralizing activity. The antitumor effects of CL were markedly inhibited by heat treatment according to the results of the tumor-neutralizing test and the 51Cr release assay, whereas heat treatment had little influence on the antitumor activity of IM-FSC. However, the neutralizing activity of effectors and the killing activity of CL against heat-treated tumor cells were both markedly augmented, since the susceptibility of the tumor cells to the antitumor effector cells was augmented by heat treatment. These results suggest that heat treatment of tumor cells augments the antitumor effects of IM-FSC and CL, hence we speculate that hyperthermia augments the effects of immunotherapy including adoptive immunotherapy.
为了研究热疗与包括过继性免疫疗法在内的免疫疗法的联合效果，我们检测了热处理对肿瘤细胞和抗肿瘤效应细胞的影响。将与BALB/c小鼠同基因的浆细胞瘤MOPC104E用作肿瘤细胞系，而将免疫于MOPC104E的新鲜脾细胞（IM-FSC）以及由IM-FSC体外诱导产生的白细胞介素-2培养淋巴细胞（CL）用作效应细胞。肿瘤细胞或效应细胞在42℃水浴中热处理30或60分钟。在肿瘤转移试验中，42℃热处理30分钟的肿瘤细胞暂时生长，然后消退，而未处理的肿瘤细胞在任何条件下均未出现消退。此外，接种来自消退肿瘤的热处理肿瘤细胞的小鼠新鲜脾细胞表现出显著的肿瘤中和活性。根据肿瘤中和试验和51Cr释放试验的结果，热处理显著抑制了CL的抗肿瘤作用，而热处理对IM-FSC的抗肿瘤活性影响很小。然而，由于热处理增强了肿瘤细胞对抗肿瘤效应细胞的敏感性，效应细胞的中和活性以及CL对热处理肿瘤细胞的杀伤活性均显著增强。这些结果表明，肿瘤细胞的热处理增强了IM-FSC和CL的抗肿瘤作用，因此我们推测热疗增强了包括过继性免疫疗法在内的免疫疗法的效果。
