title: Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs.
abstract: OBJECTIVE
  Cancer-specific immunotherapy holds great promise as an emerging treatment for advanced colorectal cancer and may be combined with standard chemotherapy to provide a synergistic inhibitory action against tumor cells. To examine the interrelationship between the immune system and chemotherapy, we studied the induction of both CEA, a tumor-associated antigen, and MHC class I, a major component of the antigen presenting system, in response to a number of chemotherapeutic agents.
  
  
  METHODS
  The effect of a selection of standard chemotherapeutics on MHC class I and CEA expression in human colorectal cancer cell lines was determined by flow cytometry and semi-quantitative RT-PCR. In addition, studies using mice bearing tumors derived from an injected murine colon cancer cell line were performed to determine if alteration in MHC class I expression occurs in vivo following continuous infusion of chemotherapeutic agents into the peritoneal cavity, as well as to facilitate correlations between expression of this factor and therapeutic effectiveness.
  
  
  RESULTS
  All anti-cancer drugs examined, when given at IC50 values, induced expression of MHC class I protein in the human colon cancer cell line, COLO201. However, expression of CEA mRNA was only induced upon exposure to 5-FU, in contrast to obscure induction following CDDP and SN-38 treatment. Combined treatment with 5-FU and CDDP gave additional effect on CEA expression in COLO201 cells. Regarding the in vivo studies in mice, the size of the murine colon cancer cell-derived tumors was reduced only in response to treatment with CDDP, which also mediated the highest induction of MHC class I expression.
  
  
  CONCLUSIONS
  These results suggest that chemotherapeutic agents trigger the immune system and cancer-specific immunotherapy may be effective when used in combination with systemic chemotherapy.
authors.affiliation: Department of Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan.
authors.forename: Shunroh
authors.initials: S
authors.lastname: Ohtsukasa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okabe
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamashita
authors.forename: Takehisa
authors.initials: T
authors.lastname: Iwai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005805:Genes, MHC Class I / Q000187:drug effects*; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000077146:Irinotecan; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin