Harvard researchers have shown that a diet rich in omega-3 fatty acids enhances immunotherapy response in mouse models of bladder cancer, lung cancer, and melanoma.
They also revealed that consumption of high levels of omega-6 fatty acids—common in American diets—was associated with a poor response to immunotherapy that could be overcome with the addition of an anti-inflammatory therapy that inhibits the enzyme soluble epoxide hydrolase (sEH).
Lead author Abigail Kelly, a research assistant at Harvard Medical School’s Beth Israel Deaconess Medical Center in Boston, presented the findings at the Experimental Biology 2022 meeting.
She told Inside Precision Medicine: “It is well-documented that inflammation in the tumor microenvironment can contribute to cancer progression. We hypothesized that increasing systemic omega-3s could promote the resolution of inflammation in the tumor microenvironment, making the tumor more likely to respond to immunotherapy.”
To investigate, Kelly and colleagues fed mice with a standard diet, a high omega-3 diet, or a high omega-6 diet for 10 days before inoculating them with bladder, lung, or skin cancer cells. The mice continued with their respective diets and began treatment a week later with immunotherapy (an anti-CTLA4 or anti-PD1 monoclonal antibody), anti-inflammatory therapy (the sEH inhibitor TPPU), or a combination of the two. In addition, there was a control group that received no treatment at all.
The researchers found that, after 10 days of treatment, tumor volume was significantly lower in mice given the omega-3 rich diet plus immunotherapy relative to those given a standard diet with immunotherapy in models of both bladder cancer and lung cancer.
Furthermore, the combination of immunotherapy plus anti-inflammatory therapy resulted in synergistic antitumor activity in mice on the high omega-3 diet, with up to 67% of tumor growth inhibited compared with mice receiving no treatment.
By contrast, Kelly and team observed substantially accelerated growth of lung cancer cells in the mice given the omega-6 rich diet plus immunotherapy. In this case tumor volume was 225% larger after 15 days of treatment compared with the mice that received no treatment.
However, the results were reversed in the mice given both immunotherapy and anti-inflammatory therapy where bladder and skin tumor growth were “dramatically reduced” compared with each drug alone and with no therapy.
“These results are encouraging especially because the omega-6 rich diet is representative of the typical western diet implying that the combination of an sEH inhibitor with immunotherapy could be clinically relevant,” Kelly reported at a press conference.
She said that overall the findings suggest that “dietary supplementation with omega- fatty acids could improve the efficacy of immunotherapy treatment.”
“Additionally, immunotherapy and sEH inhibition exhibit synergistic anti-tumor activity in mice on high omega-6 diets.”
Kelly noted that although the data are promising they need to be validated in humans. Before this is done, the researchers are planning on conducting more studies to determine the mechanism of action of how boosting omega-3s can improve immunotherapy. They are carrying out these studies in human cancer tissues and cells, human immune cells, and animal models to aid with translation to cancer patients.
