Metabolites and Immune Response in Tumor Microenvironments

SIMPLE SUMMARY: Cancer cells alter their metabolisms to support growth, thus causing micro- and macronutrient changes in the metabolite profile that promote an immunosuppressive tumor microenvironment. Immune cells and stromal cells contribute to an immunosuppressive microenvironment by releasing metabolites, cytokines, and depositing extracellular matrix that prevents lymphocyte activation and recruitment and promotes T-cell exhaustion. In recent years, new dietary interventions such as calorie restriction and periodic fasting have been shown to have beneficial effects in preventing cancer and extending life expectancy in mouse models through modulation of immune system functions. In this review, we discuss how dietary interventions such as periodic fasting can manipulate tumor metabolism, prevent the formation of an immunosuppressive microenvironment, and enhance the efficacy of anti-tumor therapies. ABSTRACT: The remodeled cancer cell metabolism affects the tumor microenvironment and promotes an immunosuppressive state by changing the levels of macro- and micronutrients and by releasing hormones and cytokines that recruit immunosuppressive immune cells. Novel dietary interventions such as amino acid restriction and periodic fasting mimicking diets can prevent or dampen the formation of an immunosuppressive microenvironment by acting systemically on the release of hormones and growth factors, inhibiting the release of proinflammatory cytokines, and remodeling the tumor vasculature and extracellular matrix. Here, we discuss the latest research on the effects of these therapeutic interventions on immunometabolism and tumor immune response and future scenarios pertaining to how dietary interventions could contribute to cancer therapy.