Kumar S, Deepak P, Acharya A
Immunology Laboratory, Banaras Hindu University, Varanasi.
Neoplasma. 2007;54(2):113-22.
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-gamma production. In contrary, Hsp70 significantly enhanced IL12, IL-15, IL-1 and IFN-gamma production by TAMs in vitro and in vivo, but also enhanced the LPS and IFN-gamma 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-gamma in TAMs without T-cells, and increased level of IFN-gamma 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.
肿瘤进展会在荷瘤宿主（TBH）中产生巨噬细胞的免疫调节表型，这些巨噬细胞通过增加可溶性因子的产生来介导免疫抑制。这些因子明显抑制T细胞反应性以及Th1极化细胞因子的产生不足。在此，我们报道用从荷DL小鼠中纯化的自体Hsp70对肿瘤相关巨噬细胞（TAM）进行体外处理可逆转肿瘤诱导的巨噬细胞抑制活性，这表明Hsp70可以恢复TAM产生Th1极化细胞因子的能力。脂多糖（LPS）刺激未能克服肿瘤诱导的IL-1、IL-12、IL-15和干扰素-γ产生的失调。相反，Hsp70在体外和体内均显著增强了TAM产生IL12、IL-15、IL-1和干扰素-γ的能力，而且还增强了TAM对LPS和干扰素-γ的反应性。TAM细胞因子的这些Th1极化作用是剂量依赖性的，在孵育24小时时达到最大值。不过，我们发现没有T细胞的TAM中有显著的干扰素-γ释放，而有T细胞时干扰素-γ水平升高表明Hsp70刺激了T细胞。总之，这些数据表明Hsp70可恢复TBH中Th1极化细胞因子的产生，因此有可能通过使用TAM开发一种新的免疫治疗方案，这可能有助于纠正肿瘤诱导的免疫功能障碍。
