Prostaglandin E2 (PGE2), a product of COX-2, can activate MDSCs via STAT3 phosphorylation, leading to suppressed CD8+ T-cell proliferation, reduced cytotoxicity against tumor cells, and impaired macrophage phagocytosis of cancer cells through the EP4-PI3K-Akt-ND-1 signaling pathway (243–250). Here, CD8A is linked to cancer.