title: The key role of calreticulin in immunomodulation induced by chemotherapeutic agents.
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.
authors: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, N-15 W-17, Sapporo, 060-0815, Japan.
authors: Yoshiyuki
authors: Y
authors: Yamamura
authors: Takahiro
authors: T
authors: Tsuchikawa
authors: Kengo
authors: K
authors: Miyauchi
authors: Shintaro
authors: S
authors: Takeuchi
authors: Masataka
authors: M
authors: Wada
authors: Toshihiko
authors: T
authors: Kuwatani
authors: Noriaki
authors: N
authors: Kyogoku
authors: Aki
authors: A
authors: Kuroda
authors: Takehiro
authors: T
authors: Maki
authors: Toshiaki
authors: T
authors: Shichinohe
authors: Satoshi
authors: S
authors: Hirano
mesh_terms: D000818:Animals; D000954:Antigens, Surface; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000032:analysis; D037282:Calreticulin / Q000276:immunology / Q000378:metabolism*; D002166:Camptothecin / Q000494:pharmacology / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D018655:Lymphocyte Count; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000494:pharmacology / Q000627:therapeutic use; D008942:Mitoxantrone / Q000494:pharmacology / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D021381:Protein Transport / Q000187:drug effects*; D013601:T-Lymphocytes / Q000737:chemistry*; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D017252:CD3 Complex; D037282:Calreticulin; D015395:Histocompatibility Antigens Class I; D003841:Deoxycytidine; D016685:Mitomycin; D008942:Mitoxantrone; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine