Abstract Summary: In this issue of Cancer Discovery, Pelly and colleagues show that inhibition of prostaglandin E2 synthesis or its activity on EP2 and EP4 receptors synergizes with anti–PD-1 immunotherapy and triggers a potent intratumoral IFNγ response in mouse models and in fresh surgical human tumor explants. This therapeutic strategy is in line with other interventions that aim at fostering immunotherapy by means of quenching protumor inflammation. See related article by Pelly et al., p. 2602.