Our recent work has revealed a superior capacity of tumor-initiating stem cells to survive from robust immunotherapy treatment and to drive tumor relapse. Built on these previous findings, another important research direction of Miao lab is to systematically decipher the immune evasive mechanisms unique to tumor-initiating stem cells in various epithelial cancers. Our research focuses on 1) how do these highly plastic cells reprogram their epigenome and metabolisms to achieve intrinsic immune resistance; 2) how do these stem cell-like cancer cells shape their microenvironment, including the immune cells and microbiome within their niche, to drive cancer immune evasion and cancer relapse from immunotherapy 3) how do various oncogenic events, such as driver mutations, and oncogenic transcription factors impact the stem cell-immune cells dialogues. The ultimatte  goal of our research is to develop novel cancer immunotherapy to blunt the stem cell-specific immune resistance with the potential of overcoming cancer relapse.