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

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 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 (SUVMax, SUVTotal, SUVMean, 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 SUVMax was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other 18F-FDG PET parameters. Increased SUVMax 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 SUVMax identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that 18F-FDG SUVMax 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.

• Authors: Kyle G Mitchell, Behrang Amini, Yunfei Wang, Brett W Carter, Myrna C B Godoy, Edwin R Parra, Carmen Behrens, Pamela Villalobos, Alexandre Reuben, J Jack Lee, Annikka Weissferdt, Cesar A Moran, Junya Fujimoto, Boris Sepesi, Garrett L Walsh, Ara A Vaporciyan, Wayne L Hofstetter, William N William Jr, Don L Gibbons, Jing Wang, Patrick Hwu, Stephen G Swisher, David Piwnica-Worms, Humam Kadara, Ignacio I Wistuba, John V Heymach, Weiyi Peng, Tina Cascone
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 69 Issue 8 Pg. 1519-1534 (Aug 2020) ISSN: 1432-0851 [Electronic] Germany
• PMID: 32300858 (Publication Type: Journal Article)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• Radiopharmaceuticals
• Fluorodeoxyglucose F18

Topics

• B7-H1 Antigen (genetics, metabolism)
• Biomarkers, Tumor (analysis)
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, immunology, metabolism, surgery)
• Fluorodeoxyglucose F18 (metabolism)
• Glycolysis
• Humans
• Lung Neoplasms (diagnostic imaging, immunology, metabolism, surgery)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Positron-Emission Tomography (methods)
• Prognosis
• Radiopharmaceuticals (metabolism)
• Retrospective Studies
• Survival Rate
• Transcriptome
• Tumor Microenvironment (immunology)