(P18-012-25) Oxylipins in the Regulation of Immune Responses: Secondary Analysis From the Docosahexaenoic Acid (DHA) for Women With Breast Cancer in the Neoadjuvant Setting (DHA WIN) Trial

Objectives: Oxylipins are immune cell signalling molecules derived from n-3 and n-6 polyunsaturated fatty acids (PUFAs) oxidation. While PUFAs are recognized for their immunomodulatory effects, the role of oxylipins in mediating immune function remains poorly understood. We previously demonstrated that supplementation with 4.4 g/day of docosahexaenoic acid (DHA) for 18 weeks during breast cancer neoadjuvant chemotherapy (NAC) preserved peripheral blood mononuclear cells (PBMCs) lipopolysaccharides (LPS)-stimulated production of TNF-α and IFN-γ. To explore mechanisms, this study investigated whether DHA supplementation alters the oxylipin profile of PBMCs. We hypothesized that DHA supplementation may enhance the immune response during NAC by stimulating cytokine production through the release of n-6 and n-3 derived oxylipins.

Methods: This is a secondary analysis of the DHA WIN controlled trial. PBMCs were isolated from whole blood (n = 10 in each group) at baseline and 15 weeks of therapy. PBMCs were stimulated ex vivo with LPS (10 µg/mL) for 48 hours to evaluate immune response, and supernatants were collected after centrifugation. Oxylipins were prepared using solid-phase extraction and quantified by liquid chromatography-mass spectrometry. Statistical significance was assessed using independent t-tests and Spearman’s correlation analysis.

Results: The total concentration of n-6 derived oxylipins significantly differed between groups, decreasing in the placebo group (20% reduction) and increasing in the DHA group (~2-fold) at 15 weeks, compared to baseline (P < 0.001). This difference was observed in most n-6 oxylipins from linoleic and arachidonic acid. As expected, n-3 derived oxylipins increased in the DHA group (~2-fold, P = 0.029) but remained unchanged in the placebo group. Within the placebo group, the concentration of total n-6 derived oxylipins at 15 weeks was positively correlated with LPS-stimulated production of TNF-α (r = 0.636, P = 0.048) and IFN-γ (r = 0.766, P = 0.010).

Conclusions: These findings suggest that the maintenance of cytokine production by PBMCs from breast cancer patients supplemented with DHA may be partially due to the production of n-6 and n-3 oxylipins.

Funding Sources: CIHR and CCI Researcher Initiated Grant. JM: scholarships from Dr. Elizabeth A. Donald, Hazel McIntyre, CRINA, and Anthony Fellowship in Human Nutrition.