Effects of glucose concentration in the tumor microenvironment on Non Small Lung Cancer (NSCLC) Progression

Abstract Lung cancer is one of the most common cancer types in the western world, with a high lethality and increasing incidence. One major factor, supporting tumor growth is a high sugar diet. Thus, reducing the sugar intake by different diets might be a way to improve current cancer treatment. These metabolic changes are accompanied by regulation of systemic levels of Insulin and insulin like growth factors. As oppose to normal cells, tumor cells metabolism mainly depends on glycolysis. Thus, reducing diet carbohydrate intake might be a way to improve current immunotherapy by inducing immunological changes caused by the extracellular glucose concentration in tumor microenvironment. Therefore, we cultured the human lung adenocarcinoma (ADC) cell line A549 with different extracellular glucose concentrations to analyze effects by flow cytometry and qPCR. Moreover, lung tissue samples from patients with non small cell lung cancer (NSCLC), were analyzed by qPCR. In a murine model of lung ADC, tumor cells were injected intravenously and mice were fed with different diets. Lung cells were isolated and analyzed by flow cytometry. Here we show that, IGF1R expression is upregulated in A549 cells line, depending on increasing extracellular glucose concentration. Moreover, in studies on human cohorts of patients with NSCLC, we found a direct correlation between BMI and IGF1R expression and its downstream signaling. Finally, in a murine model of disease, diet glucose restriction decreased significantly tumor load associated with increased lung infiltrating CD8+ T-cells and tissue-resident memory T-cells. Thus, this study supports the need to introduce glucose restrictions in the diet of patients with NSCLC in association with current immunotherapy.