Cyclooxygenase (COX)-dependent tumor growth is driven by immune evasion, as shown in a study on melanoma and other cancers. COX enzymes produce prostaglandin E2 (PGE2), which suppresses immune responses and promotes tumor growth by altering myeloid cell function. Genetic ablation of COX in tumors enables immune control and shifts the tumor inflammatory profile toward anti-cancer immune pathways. This COX-dependent inflammatory signature is conserved in human melanoma biopsies, suggesting a role in immune suppression across species. Pre-clinical data show that COX inhibition synergizes with anti-PD-1 checkpoint blockade to induce tumor eradication, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients. The study demonstrates that COX activity in tumors, particularly in Braf V600E melanoma cells, is critical for immune evasion. COX-dependent immune evasion was also critical for tumor growth in other melanoma, colorectal, and breast cancer models. Tumor immune escape could be reversed by a combination of immune checkpoint blockade and administration of COX inhibitors, suggesting that the latter may constitute useful additions to the arsenal of anti-cancer immunotherapies. COX activity in Braf V600E cells shifts the inflammatory profile at the tumor site, leading to reduced expression of tumor-promoting factors and increased expression of anti-tumor immune mediators. COX-deficient tumors showed reduced PGE2 production and increased expression of immune-related genes, indicating a shift toward anti-tumor immunity. COX-deficient tumors also showed reduced accumulation of CD103+ DCs, which are essential for anti-cancer immune responses. COX-deficient tumors were more susceptible to immune control, with immune cells such as CD8+ T cells and DCs playing a key role in tumor eradication. COX inhibition synergized with anti-PD-1 blockade to enhance tumor growth control, suggesting that COX inhibitors could be useful in combination with immune checkpoint inhibitors. The study also shows that COX activity is a key driver of adaptive immune escape by Braf V600E melanoma cells. The study highlights the importance of COX activity in tumor immune evasion and suggests that COX inhibitors could be useful in combination with immune checkpoint inhibitors for cancer treatment. The findings also indicate that COX-dependent immune evasion is a common mechanism used by cancer cells to promote immune escape across species. The study provides evidence that COX inhibitors could help unleash anti-cancer immunity and thus be useful additions to conventional and immune-based cancer therapies.Cyclooxygenase (COX)-dependent tumor growth is driven by immune evasion, as shown in a study on melanoma and other cancers. COX enzymes produce prostaglandin E2 (PGE2), which suppresses immune responses and promotes tumor growth by altering myeloid cell function. Genetic ablation of COX in tumors enables immune control and shifts the tumor inflammatory profile toward anti-cancer immune pathways. This COX-dependent inflammatory signature is conserved in human melanoma biopsies, suggesting a role in immune suppression across species. Pre-clinical data show that COX inhibition synergizes with anti-PD-1 checkpoint blockade to induce tumor eradication, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients. The study demonstrates that COX activity in tumors, particularly in Braf V600E melanoma cells, is critical for immune evasion. COX-dependent immune evasion was also critical for tumor growth in other melanoma, colorectal, and breast cancer models. Tumor immune escape could be reversed by a combination of immune checkpoint blockade and administration of COX inhibitors, suggesting that the latter may constitute useful additions to the arsenal of anti-cancer immunotherapies. COX activity in Braf V600E cells shifts the inflammatory profile at the tumor site, leading to reduced expression of tumor-promoting factors and increased expression of anti-tumor immune mediators. COX-deficient tumors showed reduced PGE2 production and increased expression of immune-related genes, indicating a shift toward anti-tumor immunity. COX-deficient tumors also showed reduced accumulation of CD103+ DCs, which are essential for anti-cancer immune responses. COX-deficient tumors were more susceptible to immune control, with immune cells such as CD8+ T cells and DCs playing a key role in tumor eradication. COX inhibition synergized with anti-PD-1 blockade to enhance tumor growth control, suggesting that COX inhibitors could be useful in combination with immune checkpoint inhibitors. The study also shows that COX activity is a key driver of adaptive immune escape by Braf V600E melanoma cells. The study highlights the importance of COX activity in tumor immune evasion and suggests that COX inhibitors could be useful in combination with immune checkpoint inhibitors for cancer treatment. The findings also indicate that COX-dependent immune evasion is a common mechanism used by cancer cells to promote immune escape across species. The study provides evidence that COX inhibitors could help unleash anti-cancer immunity and thus be useful additions to conventional and immune-based cancer therapies.