Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs

J Cancer Res Clin Oncol. 2003 Dec;129(12):719-26. doi: 10.1007/s00432-003-0492-0. Epub 2003 Oct 15.


Purpose: 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.

Conclusion: These results suggest that chemotherapeutic agents trigger the immune system and cancer-specific immunotherapy may be effective when used in combination with systemic chemotherapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Carcinoembryonic Antigen / drug effects*
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism*
  • Flow Cytometry
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, MHC Class I / drug effects*
  • Humans
  • Irinotecan
  • Mice
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation / drug effects


  • Antineoplastic Agents
  • Carcinoembryonic Antigen
  • RNA, Messenger
  • RNA, Neoplasm
  • Irinotecan
  • Cisplatin
  • Fluorouracil
  • Camptothecin