With dMMR tumor models, we focus on the three specifc questions below, aiming to solve the major clinical problems in tumor immunotherapy: 1) The majority of human tumors are lack of enough preexisting T cells, which leads to primary resistance to anti-PD1 therapy; 2) Gradually, T cells go exhausted in tumor microenvironment, especially after anti-PD1 therapy, which accounts for tumor relapse.

1. 1. The molecular mechanism of impaired innate immune surveillance in tumor cells

2. 2. Pharmacological intervention to amplify innate immune surveillance in tumor cells

3. 3. Dissect the driving factors of disfunctional T cells in tumor microenvironment

4.