Modulation of the tumor microenvironment (TME) by melatonin

The tumor microenvironment (TME) includes a number of non-cancerous cells that affect cancer cell survival. Although CD8+ T lymphocytes and natural killer (NK) cells suppress tumor growth through induction of cell death in cancer cells, there are various immunosuppressive cells such as regulatory T cells (Tregs), tumorassociated macrophages (TAMs), cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), etc., which drive cancer cell proliferation. These cells may also support tumor growth and metastasis by stimulating angiogenesis, epithelial-mesenchymal transition (EMT), and resistance to apoptosis. Interactions between cancer cells and other cells, as well as molecules released into EMT, play a key role in tumor growth and suppression of antitumoral immunity. Melatonin is a natural hormone that may be found in certain foods and is also available as a drug. Melatonin has been demonstrated to modulate cell activity and the release of cytokines and growth factors in TME. The purpose of this review is to explain the cellular and molecular mechanisms of cancer cell resistance as a result of interactions with TME. Next, we explain how melatonin affects cells and interactions within the TME.