Faculty of Life Science, Department of Molecular Pathology, Kumamoto University, Japan.
J Immunother. 2011 Jan;34(1):16-27. doi: 10.1097/CJI.0b013e3181fb03ed.
We examined the roles of a chemotherapeutic reagent in both inducing apoptosis and conferring acquired tumor immunity using mouse syngeneic tumor transplantation models. A chemotherapeutic reagent, cis-diamminedichloroplatinum (II), effectively induced apoptosis in Colon-26 cells originating from a BALB/c mouse. Three intradermal inoculations of cis-diamminedichloroplatinum (II)-treated Colon-26 cells conferred tumor immunity against viable Colon-26 cells in BALB/c mice but not in athymic BALB/c mice. The acquired immunity was Colon-26 cell specific and was adoptively transferable with splenic cells. We next examined the involvement of the cross-linked ribosomal protein S19 dimer (RP S19), which is released during apoptosis, in the acquisition of tumor immunity. A Colon-26 transformant that produces a Gln137Asn-mutant RP S19 prevents the formation of a functional RP S19 dimer. Acquired tumor immunity was significantly reduced when the transformant was used in combination with anti-RP S19 antibodies as the vaccination source. These data suggest the importance of the RP S19 dimer in chemotherapeutic agent-induced acquired immunity.
我们使用小鼠同种肿瘤移植模型，研究了一种化疗试剂在诱导细胞凋亡和赋予获得性肿瘤免疫中的作用。一种化疗试剂顺铂（cis-diamminedichloroplatinum(II)）可有效诱导源自 BALB/c 小鼠的 Colon-26 细胞凋亡。三次皮内接种经顺铂处理的 Colon-26 细胞，可使 BALB/c 小鼠获得针对活 Colon-26 细胞的肿瘤免疫力，但不能使无胸腺 BALB/c 小鼠获得该免疫力。获得的免疫力具有 Colon-26 细胞特异性，并可通过脾细胞进行过继转移。接下来，我们研究了交联核糖体蛋白 S19 二聚体（RP S19）在获得性肿瘤免疫中的作用。在凋亡过程中释放的这种交联核糖体蛋白 S19 二聚体参与了获得性肿瘤免疫。当使用产生 Gln137Asn 突变 RP S19 的 Colon-26 转化体作为疫苗来源时，获得性肿瘤免疫力显著降低。这些数据表明 RP S19 二聚体在化疗试剂诱导的获得性免疫中具有重要意义。
