Simple SummaryTumor evasion of immune surveillance is a hallmark of cancer posing challenges to effective cancer treatment. Herein we review the contributions of prostaglandins in shaping tumor microenvironments to modulate immune responses and cancer progression. Opportunities to target prostaglandins and their signaling receptors in improving cancer therapy, particularly immunotherapy, are explored.AbstractProstaglandins, the bioactive lipids generated from the metabolism of arachidonic acid through cyclooxygenases, have potent effects on many constituents of tumor microenvironments. In this review, we will describe the formation and activities of prostaglandins in the context of the tumor microenvironment. We will discuss the regulation of cancer-associated fibroblasts and immune constituents by prostaglandins and their roles in immune escapes during tumor progression. The review concludes with future perspectives on improving the efficacy of immunotherapy through repurposing non-steroid anti-inflammatory drugs and other prostaglandin modulators.