Metabolites and Immune Response in Tumor Microenvironments

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.

Integrating TCGA and Single-Cell Sequencing Data for Hepatocellular Carcinoma: A Novel Glycosylation (GLY)/Tumor Microenvironment (TME) Classifier to Predict Prognosis and Immunotherapy Response

“…At the same time, metabolic changes in tumor cells influence the activation, identification, proliferation, and cytotoxic capabilities of tumor-associated immune cells, helping them to evade immune surveillance [ 41 , 42 ]. Tumor cells alter the tumor microenvironment and help to create an immunosuppressive TME by restricting nutrients availability and by releasing metabolites, chemokines, and growth factors that reprogram the normal cell function and metabolism in TME [ 43 ].…”

The Killer’s Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer

“…Chronic inflammation and tumor-induced inflammatory responses play a key role in promoting tumorigenesis and tumor progression by modulating the differentiation of immune and stromal cells towards immunosuppressive subtypes that support immune evasion and tumor growth [ 4 , 216 ]. The release of proinflammatory cytokines, such as IL-1, IL-6, IL-8, and TNF-α, by immune, stromal, and tumor cells activates tumor proliferative and pro-survival signaling pathways, such as NF-κB and STAT3 [ 217 ].…”

“…The beneficial anti-tumor effects of CR and PF are related to the physiological changes that they induce at a systemic level, in which they decrease glucose and amino acid levels, growth hormone (GH), and insulin growth factor (IGF1) and increase the production of ketone bodies from fatty acids released following lipolysis of adipose tissue. These changes result in the inhibition of the glucose-dependent PKA/RAS protumor pathway, the IGFI- and amino acid-dependent IGFI/PI3K/AKT/mTOR pathway, activation of the AMP/ATP ratio-dependent AMPK pathway, stimulation of autophagy, and a shift in cellular metabolism from glycolysis to oxidative phosphorylation, with subsequent epigenetic reprogramming associated with changes in metabolic intermediates that act as coactivators of epigenetic enzymes [ 4 , 198 , 425 , 426 , 427 , 428 ].…”

“…This is achieved by suppressing the RAGE and IGF1 inflammatory pathways [ 438 ]. In mice with melanoma and lung cancer who underwent FMD cycles, the levels of inflammatory markers, including NLRP3 inflammasome and leukotriene, were observed to be decreased in both peripheral blood and the heart [ 4 , 439 ].…”

“…One of the contributing factors to cancer progression is persistent inflammation, which is accompanied by the production of proinflammatory cytokines that recruit myeloid cells to the tumor microenvironment. The myeloid cells then differentiate into immunosuppressive cells, thereby fostering an environment that encourages tumor growth [ 4 ]. In addition, inflammation contributes to the epigenetic remodeling of both the tumor cells and the immune system, leading to the exhaustion of T lymphocytes and the acquisition of a malignant and aggressive phenotype by the tumor cells [ 5 ].…”