Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.
Immunobiology. 2013 May;218(5):718-24. doi: 10.1016/j.imbio.2012.08.271. Epub 2012 Aug 20.
IL-17 producing CD4(+) T cells (Th17) are identified as a subset of proinflammatory T cells present at the tumor site of various murine and human cancer cases and plays a crucial role in shaping the neoplastic process through fostering tumor angiogenesis and metastasis. However, the development of Th17 response in the tumor microenvironment has not yet been fully elucidated. Herein, we make an attempt to disclose the involvement of tumor infiltrating antigen presenting cells (APCs), especially tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs) to polarize naïve CD4(+) T cells toward IL-17(+) T cells. We have found that MDSCs either isolated from the tumor site or generated in vitro are superior over TAMs to induce IL-17 production by naïve CD4(+) T cells. Furthermore, we have shown that MDSCs mediated induction of IL-17(+) T cell response is independent of MDSCs-T cell contact but crucially depends on the cytokines secreted by MDSCs. Our study will help to develop potential therapeutic strategies by harnessing the ability of MDSCs to induce IL-17 production by CD4(+) T cells and thus restrict the generation of inflammatory Th17 population at the disease site.
IL-17 产生的 CD4(+) T 细胞（Th17）被鉴定为存在于各种鼠类和人类癌症病例肿瘤部位的促炎 T 细胞亚群，通过促进肿瘤血管生成和转移，在塑造肿瘤发生过程中发挥着关键作用。然而，肿瘤微环境中 Th17 反应的发展尚未得到充分阐明。在此，我们试图揭示肿瘤浸润性抗原呈递细胞（APCs），特别是肿瘤相关巨噬细胞（TAMs）和髓源抑制细胞（MDSCs）在将幼稚 CD4(+) T 细胞向 IL-17(+) T 细胞极化中的作用。我们发现，与 TAMs 相比，源自肿瘤部位或体外生成的 MDSCs 更能诱导幼稚 CD4(+) T 细胞产生 IL-17。此外，我们还表明，MDSCs 介导的 IL-17(+) T 细胞反应的诱导不依赖于 MDSCs-T 细胞接触，而是关键依赖于 MDSCs 分泌的细胞因子。我们的研究将有助于通过利用 MDSCs 诱导 CD4(+) T 细胞产生 IL-17 的能力来开发潜在的治疗策略，从而限制疾病部位炎症性 Th17 群体的产生。
