放射线抵抗普遍存在于多种肿瘤，影响放疗疗效。我们前期工作发现低剂量姜黄素可提高射线抵抗直肠肿瘤放疗效果，但机制不清。肿瘤微环境在放射抵抗中发挥重要作用，肿瘤组织中Th17细胞参与抗肿瘤免疫，我们进一步发现姜黄素联合放疗可下调肿瘤组织EBI3表达，且肿瘤微环境中EBI3缺失促进Th17细胞分化。PD-1/PD-L1信号通路调控T细胞分化及免疫应答，由EBI3亚基组成的IL-27可诱导肿瘤及淋巴细胞PD-L1、PD-1表达。因此提出假说：姜黄素联合放疗通过下调肿瘤微环境EBI3表达，负调控PD-1/PD-L1通路，促进Th17细胞分化，发挥抗肿瘤免疫。本课题将通过体内外实验明确姜黄素联合放疗对肿瘤微环境的调节，并探索该联合治疗促进Th17细胞分化的机制。本课题的实施将丰富我们对放射肿瘤微环境中Th17细胞功能的认识，并为姜黄素作为直肠癌放疗增效剂及Th17细胞治疗联合放疗提供坚实的理论依据。

Radiation resistance exists in almost all kinds of tumor and could reduce the effect of radiotherapy. We recently discovered low dose curcumin could improve the effect of radiotherapy for radiation resistant rectal cancer, but the underling mechanism is not clear. Tumor microenvironment plays an important role in radiation resistance, and the expression of Th17 cells in tumor tissue is associated with anti-tumor immunity. We further identified that curcumin combined with radiotherapy could down regulate EBI3 expression of tumor tissue and the EBI3 knock down mice showed improved Th17 cell differentiation in tumor tissue. PD-1/PD-L1 signal pathway is involved in T cell differentiation and the regulation of immunological responses. Besides, IL-27 cytokine composed by EBI3 subunit could induce the expression of PD-L1 in tumor cells and PD-1 in T cells. Thus, we put forward the hypothesis that curcumin combined with radiation therapy could down regulate EBI3 expression in tumor microenvironment, reverse the PD-1/PD-L1 pathway mediated Th17 cell differentiation inhibition, and enhance the anti-tumor immunity. Our study will first confirm the radiation synergistic effect of curcumin with the in vitro and in vivo experiments, underline the regulation of tumor microenvironment by the curcumin and radiation combination therapy, and then explore the mechanism for the promotion of Th17 cell differentiation. Our project will rich the role of Th17 cells in the tumor microenvironment, provide a solid theoretical basis for the clinical application of curcumin as radiation synergistic agent, and the application of Th17 cell therapy combined with radiotherapy for rectal cancer treatment.