Abstract
Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor (18)F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) (18)F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUV(Max), SUV(Total), SUV(Mean), TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each (18)F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated (18)F-FDG SUV(Max) was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other (18)F-FDG PET parameters. Increased SUV(Max) was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57(+) cell density, and increased T cell exhaustion gene signature. Elevated SUV(Max) identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that (18)F-FDG SUV(Max) has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.