肿瘤免疫治疗最近在临床研究中获得重要进展，但仍然面临一些重要障碍，例如：肿瘤细胞常常存在TAP（抗原加工相关转运蛋白）或经典MHC-I类分子缺陷，致使肿瘤抗原无法正常表达，并导致肿瘤细胞逃避免疫攻击。最近，我们发现一种不依赖于TAP和经典MHC-I类分子的抗原：Hsp60信号肽（Hsp60sp）。我们曾多次报道该分子在免疫调节中的作用，并发现Hsp60sp特异性的CD8+T细胞体外能够有效杀伤TAP和经典MHC-I类分子缺失的肿瘤细胞，体内能够有效控制小鼠恶性黑色素瘤的生长。我们推测：Hsp60sp是一种肿瘤相关抗原，建立以其为靶点的免疫反应，有望重新控制那些因TAP或经典MHC-I类分子缺陷而逃逸的肿瘤细胞。本项目拟重点研究：① Hsp60sp在肿瘤细胞表面表达的机制和特点；② “针对Hsp60sp的免疫反应”的抗肿瘤作用和机制。以期阐明Hsp60sp作为肿瘤免疫治疗靶点的价值和可行性。

In spite of remarkable progress in recent years, cancer immunotherapy is still confronted with a lot of challenges, such as TAP or classic MHC-I defects in malignant cells, which lead to tumor cells escaping from immunosurveillance. Recently, we observed that Hsp60sp (Hsp60 signal peptide) specific CD8+T cells can efficently kill malignant cells carrying TAP or classic MHC-I defects, and can effectively control mice melonoma development. So, we speculate that Hsp60sp can express on cancer cells surface in a TAP and classic MHC-I independent fashion, and setting up immune reaction to Hsp60sp is expected to re-control those immune escaped tumor cells. This project aims to focus on the mechanism of Hsp60sp differential expression on tumor and normal tissues, and the anti-tumor effect and mechanism of the immune response to Hsp60sp, to clarify the value and practicability of Hsp60sp as an immune therapeutic target.