TY - JOUR
T1 - 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer
AU - Mitchell, Kyle G.
AU - Amini, Behrang
AU - Wang, Yunfei
AU - Carter, Brett W.
AU - Godoy, Myrna C.B.
AU - Parra, Edwin R.
AU - Behrens, Carmen
AU - Villalobos, Pamela
AU - Reuben, Alexandre
AU - Lee, J. Jack
AU - Weissferdt, Annikka
AU - Moran, Cesar A.
AU - Fujimoto, Junya
AU - Sepesi, Boris
AU - Walsh, Garrett L.
AU - Vaporciyan, Ara A.
AU - Hofstetter, Wayne L.
AU - William, William N.
AU - Gibbons, Don L.
AU - Wang, Jing
AU - Hwu, Patrick
AU - Swisher, Stephen G.
AU - Piwnica-Worms, David
AU - Kadara, Humam
AU - Wistuba, Ignacio I.
AU - Heymach, John V.
AU - Peng, Weiyi
AU - Cascone, Tina
N1 - Funding Information:
The authors appreciate the assistance of Mr. Alex Liu with the Division of Information Services, Oncology Care and Research IS at MD Anderson Cancer Center, and Mr. Donald Norwood with the Department of Scientific Publications at MD Anderson Cancer Center for his editorial assistance.
Funding Information:
This work was supported in part by the National Cancer Institute (5 P50 CA070907; P50 CA221703; R01 CA187076; R01 CA184845, P30CA01667), the Cancer Prevention and Research Institute of Texas (RP170401), the American Society of Clinical Oncology 2018 Career Development Award (12895), the Department of Defense (W81XWH-07-1-0306), and the Bob Mayberry Foundation. This work was also supported in part by the Bruton Endowed Chair in Tumor Biology Funds, and the generous philanthropic contributions to the University of Texas MD Anderson Cancer Center Lung Cancer Moon Shot Program, the Khalifa Scholars Program (from Khalifa Bin Zayed Al Nahyan Foundation), the Advanced Scholar Program (from CG Johnson Foundation), and the Physician Scientist Program (from T.J. Martell Foundation). Acknowledgements
Funding Information:
M.C.B. Godoy has received research funding from Siemens Healthcare. W.N. William has received honoraria/speaker’s fees and/or participated in advisory boards from Roche/Genentech, Bristol-Myers Squibb, Eli Lilly, Merck, AstraZeneca, and Pfizer. D.L. Gibbons has received research funding from AstraZeneca, Janssen, and Takeda and has participated in advisory boards for AstraZeneca and Sanofi. P. Hwu is a consultant and/or has participated in advisory boards for Immatics, Dragonfly, Sanofi, and GlaxoSmithKline. S.G. Swisher has participated in advisory committees for Ethicon and for the Peter MacCallum Cancer Center. B.S. receives consulting fees from Bristol-Myers Squibb. J.V. Heymach has received research support from AstraZeneca, Bayer, GlaxoSmithKline, and Spectrum; participated in advisory committees for AstraZeneca, Boehringer Ingelheim, Exelixis, Genentech, GlaxoSmithKline, Guardant Health, Hengrui, Lilly, Novartis, Specrtum, EMD Serono, and Synta; and received royalties and/or licensing fees from Spectrum. P. Hwu and W. Peng have received research funding in the form of grants to MD Anderson Cancer Center from GlaxoSmith Kline. T. Cascone has received speaker’s fees from the Society for Immunotherapy of Cancer and Bristol-Myers Squibb; receives consulting/advisory role fees from MedImmune, Bristol-Myers Squibb and EMD Serono, and research funding to MD Anderson Cancer Center from Boehringer Ingelheim, MedImmune and Bristol-Myers Squibb. No potential conflicts of interest are disclosed by the other authors.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Positron emission tomography
KW - Resected non-small cell lung cancer
KW - Tumor glycolysis
KW - Tumor immunometabolic phenotypes
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U2 - 10.1007/s00262-020-02560-5
DO - 10.1007/s00262-020-02560-5
M3 - Article
C2 - 32300858
AN - SCOPUS:85083786380
SN - 0340-7004
VL - 69
SP - 1519
EP - 1534
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 8
ER -