title: Aberrant T helper cell response in tumor-bearing mice limits the efficacy of dendritic cell vaccine.
abstract: Dendritic cell (DC) vaccine is a promising immunotherapy for malignancies, but its clinical efficacy has been questioned. Here we examined the mechanisms of treatment failure with DC vaccine in a murine colon cancer model. DC vaccination of naive mice prevents tumor implantation, but it is ineffective in tumor-bearing hosts despite the induction of tumor-specific CTL activity. Analyses of tumor-specific T helper cell type 1 (Th1)/T helper cell type 2 (Th2) responses showed that DC vaccine induced a mixed Th1/Th2 response in naive mice. Interestingly, CD4+ T cells from tumor-bearing mice showed a Th1-predominant response before DC vaccination but Th2 after DC vaccination. Furthermore, interleukin-10 production was higher in CD4+ T cells from vaccinated tumor-bearing mice than in CD4+ T cells from unvaccinated tumor-bearing mice. CD4+ T cells from mice treated with lipopolysaccharide (LPS)-matured DC fusion vaccine had lower production of interleukin-10 than CD4+ T cells from mice treated with non-LPS-treated DC vaccine. However, similar to the non-LPS-treated DC vaccine, the LPS-matured DC vaccine failed to suppress tumor growth and induced a Th2 predominant tumor-specific response in tumor-bearing mice. These results suggest that the presence of tumor in the host induces an aberrant CD4+ T cell response to DC vaccine, which may contribute to the failure of the vaccine to eradicate established tumors.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-0682, USA. jykao@umich.edu
authors.forename: John Y
authors.initials: JY
authors.lastname: Kao
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Chuan-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Anna
authors.initials: A
authors.lastname: Pierzchala
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007376:Interleukin-2; D008070:Lipopolysaccharides; D016753:Interleukin-10