Activation of anti-tumor immune response and reduction of regulatory T cells with Mycobacterium indicus pranii (MIP) therapy in tumor bearing mice.
Activation of anti-tumor immune response and reduction of regulatory T cells with Mycobacterium indicus pranii (MIP) therapy in tumor bearing mice.
复制标题
抗肿瘤免疫反应的激活和调节性T细胞的降低，并在伴有肿瘤轴承小鼠的inder菌（MIP）治疗中激活。
DOI：
10.1371/journal.pone.0025424
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bhaskar S
中科院分区：
文献类型：
--
作者：
Ahmad F;Mani J;Kumar P;Haridas S;Upadhyay P;Bhaskar S
免疫系统在保护宿主免受癌症侵害中的作用已得到充分证实。然而，肿瘤的生长破坏了对Th2型的免疫反应，从而逃避了宿主的抗肿瘤机制。先天和Th1型反应的激活对宿主抗肿瘤活性至关重要。在我们之前的研究中发现，在结核动物模型中，分枝杆菌（Mycobacterium indicus pranii， MIP）也被称为m.w诱导Th1型反应并激活巨噬细胞。因此，我们研究了MIP在小鼠肿瘤模型中的免疫治疗潜力及其抗肿瘤活性的潜在机制。通过皮下注射B16F10黑色素瘤细胞植入C57BL/6小鼠。采用优化的剂量和治疗方案，评价热杀MIP的抗肿瘤效果。MIP治疗组仅50-60%的小鼠出现肿瘤，肿瘤生长延迟，肿瘤体积小于对照组。分析肿瘤微环境、肿瘤引流淋巴结和脾脏中MIP介导的免疫激活。在MIP处理的小鼠中，观察到肿瘤微环境中诱导Th1反应和更高的免疫细胞浸润。表型和功能分析证实，这些免疫细胞中有很大一部分处于激活状态。有趣的是，治疗小鼠肿瘤环境中Treg细胞的百分比较低。我们还评估了MIP联合化疗的疗效，发现与单独化疗相比，MIP的疗效更好。MIP治疗对小鼠肿瘤有较好的保护作用。激活免疫细胞，增加其在肿瘤中的浸润，消除肿瘤介导的免疫抑制。
Role of immune system in protecting the host from cancer is well established. Growing cancer however subverts immune response towards Th2 type and escape from antitumor mechanism of the host. Activation of both innate and Th1 type response is crucial for host antitumor activity. In our previous study it was found, that Mycobacterium indicus pranii (MIP) also known as M. w induces Th1 type response and activates macrophages in animal model of tuberculosis. Hence, we studied the immunotherapeutic potential of MIP in mouse tumor model and the underlying mechanisms for its antitumor activity. Tumors were implanted by injecting B16F10 melanoma cells subcutaneously into C57BL/6 mice. Using the optimized dose and treatment regimes, anti-tumor efficacy of heat killed MIP was evaluated. In MIP treated group, tumor appeared in only 50–60% of mice, tumor growth was delayed and tumor volume was less as compared to control. MIP mediated immune activation was analysed in the tumor microenvironment, tumor draining lymph node and spleen. Induction of Th1 response and higher infiltration of immune cells in the tumor microenvironment was observed in MIP treated mice. A large fraction of these immune cells were in activated state as confirmed by phenotypic and functional analysis. Interestingly, percentage of Treg cells in the tumor milieu of treated mice was less. We also evaluated efficacy of MIP along with chemotherapy and found a better response as compared to chemotherapy alone. MIP therapy is effective in protecting mice from tumor. It activates the immune cells, increases their infiltration in tumor, and abrogates tumor mediated immune suppression.
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