I have always been intrigued by how cancer escape clearance by host immunity or therapeutic agents. To answer this question, I designed and performed multiple CRISPR library screenings in engrafted tumors with different immune selection, cancer-immune cell co-cultures and drug-induced cytotoxicity systems. I identified the core microRNA machinery (Nature Communications, 2021) or the epigenetic regulator KDM6A-KMT2D complex (In Submission) as key cancer-intrinsic modulators of response to T cell-mediated immunity and immunotherapy from tumor evolution. Also, I uncovered the regulation of CRBN level and CRL4^CRBN E3 ubiquitin ligase activity by COP9 signalosome (Leukemia, 2019) and another E3 ligase SCF^Fbxo7 (Plos Genetics, 2018), indicating a critical role of such regulation for immunomodulatory drugs and their derivates (PROTAC and molecular glue degraders) to induce oncoprotein degradation and cytotoxicity. As a recognition of my research achievements, I have been awarded Super Post-doctoral Fellowship of Shanghai City, General and Special Programs of Postdoctoral Science Foundation of China, and National Natural Science Foundation of China for Young Scholar.