PSGL-1高表达调节性T细胞在非小细胞肺癌免疫调节平衡中的作用及其机制

一种高表达免疫检查点调节器PSGL-1的调节性T细胞（Treg）较其他Treg表现出更强的免疫抑制功能，可能具有重要的促瘤作用。我们前期研究首次发现PSGL-1highTreg存在于非小细胞肺癌（NSCLC）患者胸腔积液中，并可明显抑制效应T细胞功能，推测该PSGL-1highTreg可能在PSGL-1介导下增强免疫抑制作用，与肺癌预后不良有关。另有研究表明PSGL-1highTreg升高可能与IL-15有关。在此基础上我们拟进行：一、分析NSCLC胸腔积液、外周血与组织标本中PSGL-1highTreg水平与临床预后关系；二、体外功能研究；三、明确PSGL-1对PSGL-1highTreg免疫功能的影响；四、探讨IL-15在肿瘤微环境中对PSGL-1highTreg水平和功能的影响；五、阐释PSGL-1highTreg在体内发挥免疫抑制的机制。为寻找NSCLC免疫治疗新靶点提供理论依据。

A subgroup of Treg, with high expression of immune checkpoint regulator PSGL-1, mediated more potent immunosuppression than other Tregs and may play an important role in tumor development. The PSGL-1high Treg were first detected in pleural effusion of non-small cell lung cancer (NSCLC) patients. It could also obviously inhibit the activity of effector T cells. We speculate that PSGL-1high Treg may possess enhanced immunosuppressive activity through PSGL-1. In addition, other researches indicated that elevated ratio of PSGL-1high Treg may associated with IL-15. The present study will extend our previous work and will: (1) analyze the relationship between clinical outcome and the distribution of PSGL-1high Treg in pleural effusion, peripheral blood and tumor tissue of NSCLC patients; (2) detect PSGL-1high Treg function in vitro. (3) clear the impact of PSGL-1 in PSGL-1high Treg. (4) explore the influence of IL-15 on PSGL-1high Treg ratio and function. (5) elucidate the immunosuppression mechnism of PSGL-1high Treg in vivo. The accomplishment of this study will provide a theoretical basis for potential means of NSCLC immunotherapy.