Nutritional modulation of antitumor immunity

Abstract

The composition and quantity of food we eat have a drastic impact on the development and function of immune responses. In this review, we highlight defined nutritional interventions shown to enhance antitumor immunity, including ketogenic, low-protein, high-fructose, and high-fiber diets, as well as dietary restriction. We propose that incorporating such nutritional interventions into immunotherapy protocols has the potential to increase therapeutic responsiveness and long-term tumor control in patients with cancer.

Figure 1.. Nutritional modulation of anti-tumor immunity.

Dietary regimens such as restricting food intake without malnutrition, or altering dietary composition, can enhance tumor control by boosting immune responses. In the case of T lymphocytes, calorie restriction, fasting-mimicking diet (FMD), or calorie-restriction mimetics can support the effector function of CD8⁺ T cells and reduce the abundance of Treg cells in tumors. Mechanistically, acetate produced by the gut microbiota during calorie restriction boosted anti-tumor responses of CD8⁺ T cells. Further, cancer cell-intrinsic signaling via insulin-like growth factor 1 (IGF-1) receptor suppresses tumor progression in the context of an FMD, which is associated with increased intra-tumoral CD8⁺ T cells and reduced Treg cells. In the setting of a low protein diet, tumor-infiltrating CD8⁺ T and NK cells become enriched, while ketone bodies produced during a ketogenic diet enhance the production of anti-tumor cytokines by CD8⁺ and CD4⁺ T cells, thereby improving tumor control. Last, implementing a high-fiber diet induces an alteration in the composition and function of the intestinal microbiota, which enhances the infiltration of CD4⁺ and CD8⁺ T cells and their capacity for anti-tumor cytokine production. The bottom panel lists the cancer therapies shown to enhance immune-mediated tumor control by the indicated nutritional intervention.