Matsubara H, Koide Y, Sugaya M, Gunji Y, Asano T, Ochiai T, Takegana K, Sakiyama S, Tagawa M
Department of Surgery (II) School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Int J Oncol. 1998 Dec;13(6):1217-22. doi: 10.3892/ijo.13.6.1217.
We examined whether antitumor effect could be produced by retrovirally expressed human interleukin-2 (hIL-2) gene in human esophageal cancer cells (T.Tn) using immunocompromised nude mice. Loss of tumorigenicity of hIL-2-producing T.Tn (T.Tn/hIL-2) cells inoculated subcutaneously was observed in contrast to continuous tumor growth of wild-type cells, although in vitro proliferation of T.Tn/hIL-2 cells remained the same as that of wild-type cells. The antitumor effect was also evidenced by the injection of T.Tn/hIL-2 cells into established tumors of wild-type cells. The injection significantly retarded the subsequent growth of wild-type tumors. Histological examination of regressing T.Tn/hIL-2 cells revealed necrotic areas and infiltration of several types of inflammatory cells. Treatment of nude mice with anti-asialoGM1 antibody did not influence the IL-2-mediated tumor rejection. Vaccination of nude mice with irradiated T.Tn/hIL-2 cells whose secretion of hIL-2 in amount was comparable to that of unirradiated cells did not develop protective immunity. Taken together, the antitumor effect achieved in nude mice by the inoculation of T.Tn/hIL-2 cells is mediated by non-T non-natural killer cells.
我们利用免疫缺陷的裸鼠研究了逆转录病毒表达的人白细胞介素-2（hIL-2）基因在人食管癌细胞（T.Tn）中是否能产生抗肿瘤作用。与野生型细胞持续肿瘤生长形成对比的是，皮下接种产生hIL-2的T.Tn（T.Tn/hIL-2）细胞后观察到致瘤性丧失，尽管T.Tn/hIL-2细胞的体外增殖与野生型细胞相同。将T.Tn/hIL-2细胞注射到野生型细胞的已建立肿瘤中也证明了抗肿瘤作用。该注射显著延缓了野生型肿瘤随后的生长。对消退的T.Tn/hIL-2细胞进行组织学检查发现有坏死区域和几种类型炎性细胞的浸润。用抗去唾液酸GM1抗体处理裸鼠并不影响IL-2介导的肿瘤排斥。用hIL-2分泌量与未照射细胞相当的经照射的T.Tn/hIL-2细胞对裸鼠进行疫苗接种并未产生保护性免疫。综上所述，接种T.Tn/hIL-2细胞在裸鼠中实现的抗肿瘤作用是由非T非自然杀伤细胞介导的。
