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Chaperone‐rich tumor cell lysate‐mediated activation of antigen‐presenting cells resists regulatory T cell suppression
Author(s) -
Larmonier Nicolas,
Cantrell Jessica,
LaCasse Collin,
Li Gang,
Janikashvili a,
Situ Elaine,
Sepassi Marjan,
Andreansky Samita,
Katsanis Emmanuel
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0907635
Subject(s) - biology , il 2 receptor , proinflammatory cytokine , t cell , cancer research , microbiology and biotechnology , immune system , antigen presenting cell , cd8 , immunology , inflammation
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‐κB, 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.