However these results should be taken with caution because a study published in Nature found that activated Nrf2 in melanoma cells increased production of cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) leading to an “immune-cold tumor environment” which lacks response to many immunotherapies and could increase tumor malignancy (58). Here, PTGS2 is linked to neoplasm.