Neoplasma Vol.54, p.113-122, 2007
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| Title: Hsp70 induces Th1 polarization through tumor-associated macrophages in a T-cell lymphoma |
| Author: S. KUMAR, P. DEEPAK, A. ACHARYA |
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Abstract: Tumor progression produces immunoregulatory phenotype of macrophages in tumor bearing host (TBH), that mediate immunosuppression through increased production of soluble factors. These factors obviously suppress the T-cell responsiveness and underproduction of Th1-polarizing cytokines. Here, we reported that in vitro treatment of TAMs with autologous Hsp70 purified from DL-bearing mice reverse back the tumor induced macrophage suppressor activity, suggesting that Hsp70 can restore TAMs production of Th1-polarizing cytokines. LPS stimulation failed to overcome tumor-induced dysregulation of IL-1, IL-12, IL-15 and IFN-γ production. In contrary, Hsp70 significantly enhanced IL12, IL-15, IL-1 and IFN-γ production by TAMs in vitro and in vivo, but also enhanced the LPS and IFN-γ responsiveness of TAMs. These Th1 polarizing effects of cytokines of TAMs are dose dependent and reach the maximal values at 24 hrs of incubation. Though, we found a significant release of IFN-γ in TAMs without T-cells, and increased level of IFN-γ with T-cells suggests that Hsp70 stimulates T-cells. Summarizing, these data demonstrates that Hsp70 restore Th1 polarizing cytokines production in the TBH and thus ascribe a possibility to develop a novel immunotherapeutic regime by using TAMs that could contribute well to the correction of tumor induced immune dysfunction.
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| Keywords: Hsp70, IL-12, IL-15, IFN-γ, TAMs, Th1 Polarizing adjuvant |
| Year: 2007, Volume: 54, Issue: |
Page From: 113, Page To: 122 |
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