The effects of docosahexaenoic acid (DHA) on plasma cytokines, oxylipins, and tumor-infiltrating lymphocytes from women with breast cancer undergoing neoadjuvant chemotherapy in the DHA-WIN trial

Jaqueline Munhoz; Gilbert Bigras; Marnie Newell; Magaly Rivas Serna; Vera Mazurak; Susan Goruk; Anil Abraham Joy; Sunita Ghosh; Kerry S Courneya; Denise G Hemmings; Catherine J Field

doi:10.1016/j.jnutbio.2025.110025

The effects of docosahexaenoic acid (DHA) on plasma cytokines, oxylipins, and tumor-infiltrating lymphocytes from women with breast cancer undergoing neoadjuvant chemotherapy in the DHA-WIN trial

J Nutr Biochem. 2025 Jul 10:110025. doi: 10.1016/j.jnutbio.2025.110025. Online ahead of print.

Authors

Affiliations

¹ Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
² Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 1C9, Canada.
³ Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
⁴ Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada; Department of Public Health Sciences, Henry Ford Hospital, Detroit, USA.
⁵ Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB T6G 2H9, Canada.
⁶ Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T5G 0B6, Canada.
⁷ Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada. Electronic address: cjfield@ualberta.ca.

PMID: 40651709
DOI: 10.1016/j.jnutbio.2025.110025

Abstract

Background: Clinical trials on docosahexaenoic acid (DHA) supplementation and immune changes during breast cancer neoadjuvant chemotherapy (NAC) are limited. This study evaluated the impact of DHA supplementation during NAC on systemic and tumor immune modulation by assessing plasma inflammatory and cardiac damage markers, tumor-infiltrating lymphocyte (TIL) proportions, and n-6- and n-3-derived oxylipins produced in response to an ex vivo immune challenge.

Methods: Venous blood was collected at baseline, 9, and 15 weeks during NAC from participants in the DHA for Women with Breast Cancer in the Neoadjuvant Setting (DHA-WIN) trial, which compared DHA-enriched algae (4.4g/day; n=23) with a placebo (n=26) over 18 weeks. Plasma markers were measured using electrochemiluminescence assays. CD4+ and CD8+ TILs were identified in tumor tissue by immunohistochemistry, and oxylipins were quantified in the supernatant of lipopolysaccharide-stimulated peripheral blood mononuclear cells via liquid chromatography-tandem mass spectrometry.

Results: DHA supplementation resulted in greater increases in the plasma cytokines IFN-γ, TNF-α, and IL-17A compared to placebo (P-interaction < 0.05). In the DHA group, concentrations of these cytokines increased at 15 weeks compared to baseline (P<0.05). No differences were found between groups for other immune markers or the proportion of TILs. Compared to the placebo, DHA led to an overall increase in total oxylipin concentrations (P<0.05) and higher production of n-6 fatty acid-derived oxylipins, particularly prostanoids, and n-3 fatty acid-derived oxylipins, including 13-HdoHE.

Conclusion: These results suggest that DHA may enhance immune responses by promoting an increase in oxylipin and cytokine concentrations, potentially benefiting patients during breast cancer NAC.

Keywords: Omega-3 fatty acids; chemotherapy; immune system; long-chain polyunsaturated fatty acid; prostanoids.