¹⁸F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung...

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 ¹⁸F-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) ¹⁸F-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 ¹⁸F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated ¹⁸F-FDG SUV_Max was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other ¹⁸F-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 ¹⁸F-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.