IL-33在ATMPs-MTX治疗恶性胸水中介导CD8+T细胞增殖活化的作用及机制研究

恶性胸腔积液（MPE）是肺癌晚期进展的表现，缺乏有效治疗手段。我们前期首创利用自体肿瘤细胞来源微颗粒包裹甲氨蝶呤（ATMPs-MTX）的靶向肿瘤杀伤作用及免疫激活效应，开展了“ATMPs-MTX治疗MPE”的国际注册临床研究，发现ATMPs-MTX治疗MPE后胸水中IL-33水平增加，且与CD8+T细胞的数量和活化表型正相关。在此基础上，我们拟研究IL-33在ATMPs-MTX治疗MPE中介导CD8+T细胞增殖活化的作用及其机制：①临床水平探讨ATMPs-MTX治疗恶性胸水中IL-33水平与CD8+T细胞增殖活化的关系；②细胞水平验证IL-33通过调控CD8+T细胞糖酵解促进其增殖活化的机制；③MPE动物模型验证IL-33在ATMPs-MTX治疗恶性胸水中介导CD8+T细胞增殖活化的作用及机制。本研究课题为ATMPs-MTX治疗恶性胸腔积液提供新的理论依据和新的联合治疗靶点。

Malignant pleural effusions(MPE)as the advanced performance of lung cancer, is lack of efficient treatments. We have designed and registered an international clinical trial about autologous tumor cell derived microparticles packaging methotrexate (ATMPs-MTX) for the treatment of MPE firstly, by using its targeted tumor killing effect and immune activation effect. Our previous study identifies that interleukin-33 correlates with the proliferation and activation of CD8+T cells in the treatment of malignant pleural effusion by ATMPs-MTX. Thus, this investigation is about to explore the mechanisms of IL-33 mediated proliferation and activation of CD8+T cells in the treatment of malignant pleural effusion by ATMPs-MTX: ①investigating the relationships of IL-33 and CD8+T cells proliferation and activation via clinical specimens; ②validating the mechanisms that IL-33 promotes CD8+ T cells proliferation and activation by regulating its glycolysis in vitro; ③using MPE mouse models verifying the mechanisms of IL-33 promotes CD8+ T cells proliferation and activation in the treatment of malignant pleural effusion by ATMPs-MTX. It provides a new theoretical basis and a combination of therapeutic targets for the treatment of malignant pleural effusion by ATMPs-MTX.