title: Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression.
abstract: CD4(+)CD25(+) regulatory T lymphocytes (Tregs) critically contribute to the mechanisms of cancer-induced tolerance. These cells suppress anti-tumoral CD8(+) and CD4(+) T lymphocytes and can also restrain the function of APCs. We have previously documented the immunostimulatory effects of a chaperone-rich cell lysate (CRCL) anti-cancer vaccine. Tumor-derived CRCL induces tumor immunity in vivo, partly by promoting dendritic cell (DC) and macrophage activation. In the current study, we evaluated the effects of CD4(+)CD25(+)forkhead box P3(+) Tregs isolated from mice bearing 12B1 bcr-abl(+) leukemia on DC and macrophages that had been activated by 12B1-derived CRCL. CRCL-activated DC and macrophages resisted Treg suppression, as the production of proinflammatory cytokines, the activation of transcription factor NF-kappaB, and their immunostimulatory potential was unaffected by Tregs. Our results thus highlight CRCL as a powerful adjuvant endowed with the capacity to overcome tumor-induced Treg-inhibitory effects on APCs.
authors.affiliation: Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Jessica
authors.initials: J
authors.lastname: Cantrell
authors.forename: Collin
authors.initials: C
authors.lastname: Lacasse
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Elaine
authors.initials: E
authors.lastname: Situ
authors.forename: Marjan
authors.initials: M
authors.lastname: Sepassi
authors.forename: Samita
authors.initials: S
authors.lastname: Andreansky
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D007165:Immunosuppression Therapy; D007942:Leukemia, Experimental / Q000473:pathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016328:NF-kappa B