Yamamura Yoshiyuki, Tsuchikawa Takahiro, Miyauchi Kengo, Takeuchi Shintaro, Wada Masataka, Kuwatani Toshihiko, Kyogoku Noriaki, Kuroda Aki, Maki Takehiro, Shichinohe Toshiaki, Hirano Satoshi
Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N-15 W-17, Sapporo, 060-0815, Japan.
Int J Clin Oncol. 2015 Apr;20(2):386-94. doi: 10.1007/s10147-014-0719-x. Epub 2014 Jun 28.
It has recently been shown that certain chemotherapeutic agents can improve host immune responses. The present study aimed to demonstrate the mechanism by which chemotherapeutic agents modify the tumor microenvironment and induce tumor-specific immune responses.
Three mouse cancer cell lines [CT26 mouse colon cancer cells, B16 melanoma cells and Lewis lung carcinoma (LLC)], 5 human carcinoma cell lines (human esophageal squamous cell carcinoma cell lines TE8 and HEC46 and the human pancreatic carcinoma cell lines PK-9, AsPC-1 and SUIT-2) and 5 chemotherapeutic agents [mitoxantrone (MIT), mitomycin C(MMC), 5-fluorouracil (5FU), camptothecin (CPT-11) and cisplatin (CDDP)] that are frequently used in a clinical setting for cancer treatment were utilized to investigate the surface expression level of calreticulin and HLA class I after exposure to chemotherapeutic agents.
Increased calreticulin (CRT) expression on the surface of mouse cell lines and, moreover, increased surface expression levels of both CRT and HLA class I in all human cell lines were observed in cells treated by the chemotherapeutic agents as compared with non-treated cells. The surface expression level of CRT was significantly correlated with the HLA class I expression level in all human cell lines.
In conclusion, chemotherapeutic drugs can improve the immunogenicity of cancer cells in a cell-specific manner through the mechanism of translocation of CRT.
最近有研究表明，某些化疗药物可改善宿主免疫反应。本研究旨在阐明化疗药物改变肿瘤微环境并诱导肿瘤特异性免疫反应的机制。
使用三种小鼠癌细胞系[CT26小鼠结肠癌细胞、B16黑色素瘤细胞和Lewis肺癌（LLC）]、五种人类癌细胞系（人类食管鳞状癌细胞系TE8和HEC46以及人类胰腺癌细胞系PK-9、AsPC-1和SUIT-2）以及五种临床上常用于癌症治疗的化疗药物[米托蒽醌（MIT）、丝裂霉素C（MMC）、5-氟尿嘧啶（5FU）、喜树碱（CPT-11）和顺铂（CDDP）]，来研究暴露于化疗药物后钙网蛋白和HLA I类分子的表面表达水平。
与未处理的细胞相比，在经化疗药物处理的细胞中，观察到小鼠细胞系表面的钙网蛋白（CRT）表达增加，而且在所有人类细胞系中CRT和HLA I类分子的表面表达水平均增加。在所有人类细胞系中，CRT的表面表达水平与HLA I类分子表达水平显著相关。
总之，化疗药物可通过CRT易位机制以细胞特异性方式提高癌细胞的免疫原性。
