骨髓特异性ST2阳性Treg细胞通过增强HPGD酶活性影响AML进展的机制研究

急性髓系白血病（AML）是血液系统难治性恶性肿瘤。明确其发病机制并找到新的治疗靶点具重要意义。调节性T细胞（Treg）具独特的免疫抑制作用，是抗肿瘤免疫治疗的重要靶点。我们前期研究表明：生长刺激表达基因2（ST2）阳性的Treg细胞具有促进小鼠肠粘膜组织修复的作用。最近，我们发现AML患者及动物模型的骨髓Treg细胞中ST2表达水平较高，且能够抑制AML小鼠骨髓CD8+T细胞浸润，但作用机理不明。文献报道显示Treg细胞可通过调节15-羟基前列腺素脱氢酶（HPGD）活性发挥免疫抑制作用。故我们推测：骨髓特异性ST2阳性Treg细胞通过增强HPGD的活性，抑制CD8+T细胞抗肿瘤能力，从而促进AML进展。本研究拟建立AML动物模型，通过体内外试验证实上述假说。靶向骨髓肿瘤微环境中Treg细胞上的ST2分子可为AML的免疫治疗提供新的靶点和临床治疗策略。

Acute myeloid leukemia (AML) is a refractory hematological malignancy. Investigating the mechanism and therapeutic targets are critical for AML treatment. Regulatory T cell (Treg) displays unique immune suppressive effect in tumor progression and is a novel target for tumor immunotherapy. We have previously demonstrated that ST2+Tregs located in specific organs were able to maintain homeostasis. Our preliminary data showed that the bone marrow Tregs from both AML patients and mice exhibited elevated level of ST2 expression. AML mice lack of ST2+Tregs showed more CD8+T cells infiltration and decreased proliferation of tumor cells in the bone marrow. Enzymatic activity of 15- hydroxyprostaglandin dehydrogenase (HPGD) in Tregs has recently been shown to suppress T conventional cells in adipose tissue. Here we decided to investigate if ST2+Tregs are specifically localized in bone marrow niche and promote the progression of AML through regulating the enzyme activity of HPGD. ST2 blockade on Tregs in tumor microenvironment could serve as a new immunotherapy avenue for AML treatment.