Uekusa Yasuhiro, Gao Ping, Yamaguchi Nobuya, Tomura Michio, Mukai Takao, Nakajima Chigusa, Iwasaki Masayuki, Takeuchi Noritame, Tsujimura Takahiro, Nakazawa Mitsuhiro, Fujiwara Hiromi, Hamaoka Toshiyuki
Department of Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
J Leukoc Biol. 2002 Nov;72(5):864-73.
Interleukin (IL)-12 plays a central role in the initiation and regulation of T cell-mediated immune responses. The present study investigated how IL-12, endogenously produced during tumor vaccination, functions for anti-tumor immune responses. Mice were given anti-IL-12 monoclonal antibody during immunization with attenuated syngeneic tumor cells. Splenic T cells from anti-IL-12-treated immunized mice exhibited comparable levels of tumor-neutralizing activity with those from tumor-immunized mice without anti-IL-12 treatment. When these two groups of mice were directly challenged with viable tumor cells, tumor rejection was induced only in anti-IL-12-untreated mice. T cell infiltration was observed at the site of tumor challenge in these mice, whereas such a T cell infiltration did not occur in anti-IL-12-treated mice. The tumor-migratory capacity was directly assessed by transferring spleen cells from tumor-immunized mice into syngeneic, tumor-bearing recipient mice and by quantitating donor cells migrating into recipients' tumor masses. T cells from anti-IL-12-treated tumor-immunized mice were found to exhibit a markedly reduced tumor-migratory capacity when compared with that of anti-IL-12-untreated mice. Moreover, the migration of T cells from anti-IL-12-untreated mice to tumor masses prepared in anti-IL-12-treated mice was severely reduced. These results indicate that endogenously produced IL-12 has dual roles in anti-tumor-immune resistance: One is to confer T cells with a tumor-migratory capacity, and the other is to allow tumor masses to develop the capacity to accept tumor-migrating T cells.
白细胞介素（IL）-12在T细胞介导的免疫反应的启动和调节中发挥着核心作用。本研究调查了肿瘤疫苗接种过程中内源性产生的IL-12如何发挥抗肿瘤免疫反应的功能。在用减毒同基因肿瘤细胞免疫小鼠的过程中给予抗IL-12单克隆抗体。来自抗IL-12处理的免疫小鼠的脾T细胞与未接受抗IL-12处理的肿瘤免疫小鼠的脾T细胞表现出相当的肿瘤中和活性水平。当这两组小鼠直接用活的肿瘤细胞攻击时，只有未接受抗IL-12处理的小鼠诱导出肿瘤排斥反应。在这些小鼠的肿瘤攻击部位观察到T细胞浸润，而在接受抗IL-12处理的小鼠中未发生这种T细胞浸润。通过将肿瘤免疫小鼠的脾细胞转移到同基因的荷瘤受体小鼠中，并定量迁移到受体肿瘤块中的供体细胞，直接评估肿瘤迁移能力。与未接受抗IL-12处理的小鼠相比，发现来自接受抗IL-12处理的肿瘤免疫小鼠的T细胞表现出明显降低的肿瘤迁移能力。此外，未接受抗IL-12处理的小鼠的T细胞向接受抗IL-12处理的小鼠制备的肿瘤块的迁移严重减少。这些结果表明，内源性产生的IL-12在抗肿瘤免疫抵抗中具有双重作用：一是赋予T细胞肿瘤迁移能力，二是使肿瘤块发展出接受肿瘤迁移T细胞的能力。
