In tumor microenvironment (TME), active inflammation occurs with immunosuppression. The former promotes tumor growth and the latter facilitates evasion of tumor cells from immune surveillance. Given that active inflammation generally induces acquired immunity, how immunosuppression is elicited in actively-inflamed TME remains an enigma. Immune cells infiltrating the tumor, stromal cells activated in TME and tumor cells themselves produce and secrete various mediators, which are supposed to trigger inflammation and elicit immunosuppression. We have examined the role of prostaglandin E2 (PGE2) in this process bidirectionally by both translational and reverse translational research. As a translational research, we have used mouse syngeneic tumor models, and interfered with PGE2 signaling with EP2 and EP4 antagonists. As a reverse translation research, we have obtained surgical specimen of human tumors, dissociated them and sorted EP4-positive immune cells in TME. In both researches, we have employed single cell RNA sequencing technology, which allows us to identify the immune landscape, phenotypic changes and cell-cell communications dependent on these EP receptors in an unbiased way. The findings obtained by these researches are presented and the validity of this approach is discussed.