Three recent studies revealed synergy between immune-checkpoint inhibitors and the microbiome as a new approach in the treatment of cancer. Incidentally, there has been significant progress in understanding the role of polyunsaturated fatty acids (PUFAs) in modulating cancer and the immune system, as well as in regulating the microbiome. Inflammation seems to be the common denominator among these seemingly unrelated biological entities-immune system, the microbiome, and long-chain polyunsaturated fatty acids (LC-PUFAs). This commentary presents a hypothesis proposing the existence of an optimal level of LC-PUFAs that nurtures the suitable gut microbiota preventing dysbiosis. This synergy between optimal LC-PUFAs and gut microbiota helps the immune system overcome the immunosuppressive tumour microenvironment including enhancing the efficacy of immune checkpoint inhibitors. A model on how LC-PUFAs (such as omega(n)-3 and n-6 fatty acids) forms a synergistic triad with the immune system and the microbiome in regulating inflammation to maintain homeostasis is presented. The principles underlying the hypothesis provide a basis in managing and even preventing cancer and other chronic diseases associated with inflammation.

PMID: 30201858

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