线粒体和溶酶体不仅是细胞内能量产生和大分子降解的主要场所，也参与对胞内多种信号通路的调控，与细胞的命运决定、功能行使以及疾病发生都密切相关。近年来的研究发现线粒体和溶酶体间存在相互作用。然而，这些相互作用的调控机制以及与胞内信号和疾病发生的关系仍不清楚。iNKT细胞是肿瘤免疫治疗的重要候选细胞。我们在前期研究中发现，肿瘤中iNKT细胞功能异常。恢复iNKT细胞的功能尤其是IFNγ应答，能有效增强iNKT细胞介导的抗肿瘤免疫，抑制肿瘤细胞生长并延长小鼠存活时间。伴随着肿瘤中iNKT细胞的功能失常，细胞内线粒体和溶酶体的互作紊乱。揭示线粒体-溶酶体互作的调控机制以及其与iNKT细胞抗肿瘤功能异常的关系，不仅有利于阐释线粒体-溶酶体互作在调控细胞功能和疾病发生中的关键作用，也能促进新的药物靶点的发现，为发展新的免疫治疗策略提供依据。

Lysosome and mitochondria are more than organelles for energy production and molecule degradation. They regulate intracellular signal pathways and control the fate and functions of cells, and thus are closely related to progression of diseases. Recent studies indicate a direct and dynamic contact between lysosome and mitochondria. However, the mechanisms regulating the mitochondria-lysosome contact and the roles of the contact site in modulating intracellular signal pathways and diseases remain unclear. iNKT cells are promising candidates for immunotherapies against tumors. Our previous studies demonstrated dysfunction of intratumoral iNKT cells. Recovering their functions especially IFNγ production successfully augmented the iNKT cell-mediated anti-tumor immune responses, and thereby inhibited tumor growth and prolonged mice survival. In company with the dysfunction of iNKT cells, we observed abnormal mitochondria-lysosome contact in tumor infiltrating iNKT cells. Here, we will explore the mechanisms underlying the abnormal mitochondria-lysosome contact and demonstrate its contribution to the dysfunction of intratumoral iNKT cells. Our results will discover the significance of mitochondria-lysosome contact in controlling cell functions and diseases, and help to identify new drug targets for developing immunotherapies against tumors.