title: Immunogenic cell death due to a new photodynamic therapy (PDT) with glycoconjugated chlorin (G-chlorin).
abstract: 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.
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yano
authors.affiliation: Research Institute of Natural Sciences, Okayama University of Science, Okayama 700-0005, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Research Institute of Natural Sciences, Okayama University of Science, Okayama 700-0005, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Akashi
authors.affiliation: Department of Biochemistry, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Nishie
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Shimura
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mizoshita
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kubota
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanida
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Departments of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D006001:Glycoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin
keywords: calreticulin (CRT); glycoconjugated chlorin (G-chlorin); high-mobility group box 1 protein (HMGB1); immunogenic cell death (ICD); photodynamic therapy