Tumor cells have developed multiple mechanisms to escape immune recognition mediated by T cells. Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme inducing immune tolerance, is involved in tumor escape from host immune systems. Feiji Recipe, a Chinese herbal recipe that composed of 12 traditional Chinese medicines, has been used to recover immuno-surveillance and to interven immune escape in lung cancer patients. To elucidate the biological role of IDO in the tumorigenesis of lung cancer, and the intervention of Feiji Recipe on tumor immune escape, we established a mouse lung cancer cell line (2LL-EGFP-IDO) with overexpression of IDO. IDO expression did not affect cell proliferation. 2LL-EGFP-IDO cells were effective in reducing the level of tryptophan and increasing the level of its downstream metabolites, kynurenines, in culture medium as assessed by HPLC. Feiji Recipe could up-regulate the percentage of CD8+ T cells by inhibits the expression of IDO in co-culture system. The results of these studies indicate that Feiji Recipe can enhance the immune response and reverses tumor immune escape by induce the activity of CD8+ T cells, which might be related to the inhibition of IDO expression.
肿瘤细胞能够通过多种机制逃避T细胞介导的免疫识别,而吲哚胺2,3-双加氧酶(IDO)是一种色氨酸代谢酶,它能够通过降解色氨酸,同时产生犬尿氨酸,从而诱导免疫耐受,最终导致肿瘤细胞逃避宿主免疫杀伤。肺积方是由12位中药组成的复方,已被证实能够干预免疫逃逸,提高肺癌患者的免疫监视能力。为进一步探讨IDO在肺癌的发生发展过程中的生物学作用和肺积方对肿瘤免疫逃逸的干预机制,本研究构建了过表达IDO的小鼠肺癌细胞株(2LL-EGFP-IDO)。IDO的过表达不影响2LL细胞的增殖。高效液相检测结果显示2LL-EGFP-IDO细胞能够有效的代谢培养基中的色氨酸,同时产生其下游代谢产物犬尿氨酸。而共培养体系中,肺积方干预后能够抑制IDO的表达,从而上调CD8+ T细胞的比例。我们的研究表明肺积方能够通过抑制IDO的表达,上调CD8+ T细胞的比例,以增强免疫应答、逆转肿瘤细胞的免疫逃逸。