In an ovarian cancer mouse model intrinsically resistant to immune checkpoint blockade (ICB), we developed a novel radio-immunotherapy combination approach (RACIM) capable of converting "cold" immunologically desert tumors into "hot" inflamed tumors, enhancing the therapeutic efficacy of ICB. In collaboration with other groups (Hi-TIDe Denarda Dangaj group, Center of Experimental Therapeutics, and Service of Immuno-oncology), we brought our innovative radio-immunotherapy combination to the bedside and demonstrated significant therapeutic advantages for some metastatic cancer patients. Currently, we use single cell genomic approaches to understand the molecular states of immune cells and the tumor microenvironment (TME) during RACIM tumor escape or rejection in mouse and human patients. We discovered essential molecular mechanisms that caused T cell dysfunction in tumors. We believe that by addressing these processes, we will be able to remodel the immunosuppressive TME and improve the efficacy of cancer immunotherapy.