title: MC32 tumor cells acquire Ag-specific CTL resistance through the loss of CEA in a colon cancer model.
abstract: We previously reported that MC32 cells resist carcinoembryonic antigen (CEA) DNA vaccination by losing their antigen presentation to Ag-specific CTLs in the context of MHC class I antigens in a colon cancer therapeutic model. In this study, we selected 2 tumor cells, MC32-S2-2 and MC32-S4-2, which have the ability to form tumors in CEA DNA vaccine-immunized mice. Wild type MC32 cells grew significantly less in CEA-immunized mice (with Ag-specific CTL lytic activity) than in control mice (with no Ag-specific CTL lytic activity). However, MC32-S2-2 and MC32-S4-2 cells grew at a similar rate in both control and CEA-immunized mice, confirming their resistant status against CEA DNA vaccination. MC32-S2-2 and MC32-S4-2 cells were not susceptible to lysis by CEA-specific CD8+ T cells. Moreover, when MC32-S2-2 and MC32-S4-2 cells were used as stimulating agents of CEA-specific immune cells for IFN-γ production, these cells failed to stimulate the induction of Ag-specific IFN-γ, suggesting a loss of tumor cell recognition by Ag-specific immune cells. However, MC32-S2-2 and MC32-S4-2 cells expressed MHC class I antigens in a manner similar to that of wild type MC32 cells. Finally, Western blot assay confirmed that in MC32-S2-2 and MC32-S4-2 cells, CEA expression remained absent but mouse CEA was expressed. Taken together, these data show that MC32 cells may also be able to achieve resistance to CEA-specific CTLs by antigen loss in this model.
authors.affiliation: a Department of Plastic and Reconstructive Surgery ; School of Medicine; Kangwon National University ; Chuncheon , Gangwon-do , Korea.
authors.forename: Sang-Yeul
authors.initials: SY
authors.lastname: Lee
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D057131:Immune Evasion; D008810:Mice, Inbred C57BL; D009369:Neoplasms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D002272:Carcinoembryonic Antigen
keywords: Antitumor immunity; CEA; CEA, carcinoembryonic antigen; CFSE, carboxyfluorescein diacetate succinimidyl ester; DNA vaccines; EP, electroporation; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HLA, human leukocyte antigen; IM, intramuscular; LDH, lactate dehydrogenase; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; UV, ultraviolet; colon cancer; i.v., intravenously; immune evasion; s.c., subcutaneously