Fish oil attenuates surgery-induced immunosuppression, limits post-operative metastatic dissemination and increases long-term recurrence-free survival in rodents inoculated with cancer cells

Background & aims: Omega-3 fatty acids (ω-3FA) attenuate postoperative immunosuppression vis-à-vis infection. Since immune-surveillance targets metastasizing cancer cells, we assessed the effect of ω-3FA consumption on 1) early post-operative Natural Killer cell (NK) cytotoxicity and metastases and 2) long-term recurrence-free survival, in two rodent models of surgery-promoted metastases. Methods: C57BL/6J mice were fed standard, ω-3FA-enriched, or ω-6FA-enriched chow, beginning one week before subcutaneous footpad implantation of syngeneic melanoma cells. When tumors reached the volume of 110 μl, the tumor-bearing footpad was amputated, and long-term recurrence-free survival was assessed. Also, F344 rats were fed ω-3FA or ω-6FA for a month before undergoing or not undergoing laparotomy, and were intravenously inoculated with radio-labeled syngeneic adenocarcinoma cells. Marginating-pulmonary (MP)-leukocytes were harvested, and lung tumor retention (LTR) of metastases was assessed. Results: ω-3FA consumption did not affect the growth of footpad tumors, but significantly enhanced post-amputation recurrence-free survival in mice. Surgery had a deleterious effect on NK cell activity and LTR whereas ω-3FA had large beneficial effects in non-operated rats and an even greater impact in operated rats. Conclusions: ω-3FA feeding attenuates or even overcomes postoperative NK cell suppression, increases resistance to experimental and spontaneous metastasis, and enhances recurrence-free survival following excision of metastasizing primary tumors. These findings warrant clinical studies of ω-3FA-based nutrition in patients undergoing resection of a primary tumor.