Research Papers:

Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin)

Mamoru Tanaka, Hiromi Kataoka _, Shigenobu Yano, Takuya Sawada, Haruo Akashi, Masahiro Inoue, Shugo Suzuki, Yusuke Inagaki, Noriyuki Hayashi, Hirotada Nishie, Takaya Shimura, Tsutomu Mizoshita, Yoshinori Mori, Eiji Kubota, Satoshi Tanida, Satoru Takahashi and Takashi Joh

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Oncotarget. 2016; 7:47242-47251. https://doi.org/10.18632/oncotarget.9725

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Mamoru Tanaka1, Hiromi Kataoka1, Shigenobu Yano2, Takuya Sawada3, Haruo Akashi3, Masahiro Inoue4, Shugo Suzuki5, Yusuke Inagaki1, Noriyuki Hayashi1, Hirotada Nishie1, Takaya Shimura1, Tsutomu Mizoshita1, Yoshinori Mori1, Eiji Kubota1, Satoshi Tanida1, Satoru Takahashi5, Takashi Joh1

1Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

2Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan

3Research Institute of Natural Sciences, Okayama University of Science, Okayama 700-0005, Japan

4Department of Biochemistry, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan

5Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Correspondence to:

Hiromi Kataoka, email: [email protected]

Keywords: glycoconjugated chlorin (G-chlorin), photodynamic therapy, calreticulin (CRT), high-mobility group box 1 protein (HMGB1), immunogenic cell death (ICD)

Received: November 12, 2015    Accepted: May 13, 2016    Published: May 30, 2016


Both the pre-apoptotic exposure to calreticulin (CRT) and the post-apoptotic release of high-mobility group box 1 protein (HMGB1) are required for immunogenic cell death. Photodynamic therapy (PDT) uses non-toxic photosensitizers and visible light at a specific wavelength in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature, and stimulate the host immune system. We have previously shown that glycoconjugated chlorin (G-chlorin) has superior cancer cell selectivity and effectively suppresses the growth of xenograft tumors. In the present study, we evaluated the immunogenicity of PDT with G-chlorin treatment in colon cancer cells. PDT with G-chlorin suppressed CT26 (mouse colon cancer cells) tumor growth considerably more efficiently in immunocompetent mice (wild-type mice, allograft model) than in immune-deficient mice (nude mice, xenograft model), although control treatments were not different between the two. This treatment also induced CRT translocation and HMGB1 release in cells, as shown by western blot and immunofluorescence staining. To evaluate the use of PDT-treated cells as a tumor vaccine, we employed a syngeneic mouse tumor model (allograft model). Mice inoculated with PDT-treated CT26 cells were significantly protected against a subsequent challenge with live CT26 cells, and this protection was inhibited by siRNA for CRT or HMGB1. In conclusion, PDT with G-chlorin treatment induced immunogenic cell death in a mouse model, where the immunogenicity of this treatment was directed by CRT expression and HMGB1 release.

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