Fish Oil Enhances T Cell Function and Tumor Infiltration and Is Correlated With a Cancer Prevention Effect in HER-2/neu But Not PyMT Transgenic Mice

Abstract

Few studies have explored the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on immune modulation in murine models of mammary carcinogenesis. HER-2/neu and PyMT mice were randomized to 2 dietary interventions: AIN-93G-based diet with 1) 11% of diet (per gram weight) as corn oil (CO) or 2) 10% of diet as menhaden fish oil plus 1% of diet as corn oil (FO). FO significantly reduced the incidence and multiplicity of tumors (P < 0.001) in HER-2/neu, but not PyMT mice. FO-fed mice had significantly larger splenocyte counts than CO-fed mice in both the HER-2/neu and PyMT models; and in both models this was comprised of an increase in most cell types, including Gr-1(+)/CD11b(+) cells. T cells from FO-fed HER-2/neu mice produced significantly more interleukin-2 (P = 0.004) and interferon-γ (P = 0.012) in response to in vitro stimulation with anti-CD3 (0.5 µg/ml). Lastly, FO-fed HER-2/neu mice had significantly more tumor immune infiltrates than CO-fed mice, including NK1.1(+), F4/80(+), and Gr-1(+)/CD11b(+) cells (P ≤ 0.05). Greater Th1 cytokine production and significantly more tumor immune infiltrates in FO-fed Her2/neu mice may account for the cancer prevention effect of fish oil in this model.

Effects of omega-3 fatty acids on patients undergoing surgery for gastrointestinal malignancy: a systematic review and meta-analysis

“…It is essential to understand precisely how specific (n-3) PUFAs modulate immune function. Turbitt [38] suggested that it is possible that n-3 PUFAs induced an increase in IL-2 and IFN-g production in T cells, which may drive a Th1 response, enhance antitumor immunity, and contribute to the cancer prevention effect of n-3 PUFAs. Thus, n-3 PUFA supplementation may enhance Th1 cytokine response and may differentially alter the effector function of T cells.…”

Physical Activity Plus Energy Restriction Prevents 4T1.2 Mammary Tumor Progression, MDSC Accumulation, and an Immunosuppressive Tumor Microenvironment

“…Spleens were harvested and splenocytes were prepared from individual mice as described previously (22). Primary tumors were harvested during dissection, weighed, minced, and incubated with 0.03 mg/mL Liberase (Roche) and 12.5 U/mL DNase I (Sigma-Aldrich) for 45 minutes at 37 C. Following digestion, remaining pieces were mechanically disrupted, passed through a 70-mm nylon mesh strainer (BD Biosciences), layered over Lympholyte-M cell Separation Media (Cedarlane), and centrifuged at room temperature for 20 minutes at 1,200 Â g. Isolated cells were washed in cold PBS (Mediatech) and cell counts and viability were determined via Trypan Blue exclusion.…”

Increased Adiposity Enhances the Accumulation of MDSCs in the Tumor Microenvironment and Adipose Tissue of Pancreatic Tumor-Bearing Mice and in Immune Organs of Tumor-Free Hosts

“…Spleens, tumor-draining lymph nodes (TDLN), and tumors were harvested, and single-cell suspensions were prepared as previously described [6,40]. Cell counts and viability were determined via trypan blue exclusion (Corning; Tewksbury, MA, USA).…”

“…Single cell suspensions of splenocytes, TDLN, and tumor-infiltrating immune cells were washed twice in PBS containing 0.01% bovine serum albumin at 4 • C. Cells were incubated with Fc block (Biolegend; San Diego, CA, USA) and stained with saturating concentrations of conjugated antibodies, listedin Supplemental Table S2, as previously described [6,40]. Lymphoid and myeloid cells were gated on forward vs. side scatter, and a total of 30,000 events were acquired.…”