Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression.
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.
Larmonier
Nicolas
N
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA.
Cantrell
Jessica
J
Lacasse
Collin
C
Li
Gang
G
Janikashvili
Nona
N
Situ
Elaine
E
Sepassi
Marjan
M
Andreansky
Samita
S
Katsanis
Emmanuel
E
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*
D016328:NF-kappa B