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01-08-2020 | NSCLC | Original Article

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

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

Published in: Cancer Immunology, Immunotherapy | Issue 8/2020

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 (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.

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Title: 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer
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
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Positron Emission Tomography
Published in: Cancer Immunology, Immunotherapy / Issue 8/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02560-5

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