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01.04.2015 | Original Article | Ausgabe 2/2015

International Journal of Clinical Oncology 2/2015

The key role of calreticulin in immunomodulation induced by chemotherapeutic agents

Zeitschrift:
International Journal of Clinical Oncology > Ausgabe 2/2015
Autoren:
Yoshiyuki Yamamura, Takahiro Tsuchikawa, Kengo Miyauchi, Shintaro Takeuchi, Masataka Wada, Toshihiko Kuwatani, Noriaki Kyogoku, Aki Kuroda, Takehiro Maki, Toshiaki Shichinohe, Satoshi Hirano

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

In conclusion, chemotherapeutic drugs can improve the immunogenicity of cancer cells in a cell-specific manner through the mechanism of translocation of CRT.

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