Omega-3 fatty acid supplementation – A possible dietary adjunct to enhance immune checkpoint inhibition therapy in cancer?

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been found to be modulators of immune function. Additionally, they may affect the growth of colorectal cancer (CRC). With the advent of novel treatment approaches in oncology targeting immune checkpoint inhibition and aiming to boost the immune re sponse against tumors the exact role of n-3 and n-6 PUFA in inflammation as well as in CRC needs to be re-evaluated in order to understand potential interactions with these new treatment options. Interestingly, for the cyclooxygenase (COX) inhibitor aspirin a possible synergistic effect together with an anti-programmed cell death protein-1 (anti-PD-1) antibody has been shown. However, could high n-3 PUFA be disadvantageous in the context of immune therapy due to an immune suppressive effect that has been described for these fatty acids in the past, or could they also enhance the effect of immune checkpoint inhibition? In this paper, we explore this topic and show in a small experimental series that incubation of human peripheral blood mononuclear cells (PBMCs) with the n-3 PUFA docosahexaenoic acid (DHA) significantly decreases CRC-cell supernatant-triggered secretion of IL-10 and increases secretion TNF-α, while the n-6 PUFA arachidonic acid (AA) reduced TNF-α secretion. These changes in cytokine secretion upon incubation with DHA thus indicate a possible enhancing effect of n-3 PUFA on an anti-tumor immune response.