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Original research
Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor
Kyoichi Kaira
Saitama University Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5548-7686
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
2-Deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (18F-FDG-PET) is a convenient modality to assess metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs.
Methods
A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C and β2 adrenergic receptor.
Results
High uptakes of SUVmax, SUVmean, MTV and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%) and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS of 1-2, thymic carcinoma and advanced stage, and SUVmax on 18F-FDG uptake displayed a close association with PD-L1 and PD-L2 expression, but not MTV and TLG. Multivariate analysis revealed that SUVmax was identified as an independent predictor for positive PD-L1 /PD-L2 expression. GLUT1 was clarified as a significant marker for the expression of PD-L1/PD-L2 from the biological viewpoint.
Conclusion
18F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect glucose metabolism and hypoxia in thymic tumor cells.
Keywords
PD-L1, PD-L2, GLUT1, HIF-1α, 18F-FDG uptake, thymic epithelial tumor, immunohistochemistry
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CURRENT STATUS: Under Review
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Review #4 received
Received 10 Jan, 2021
Editorial decision: Major Revision
On 10 Jan, 2021
Review #3 received
Received 09 Jan, 2021
Reviewer #4 agreed
On 30 Dec, 2020
Reviewer #3 agreed
On 30 Dec, 2020
Review #2 received
Received 26 Dec, 2020
Review #1 received
Received 25 Dec, 2020
Reviewer #2 agreed
On 15 Dec, 2020
Reviewer #1 agreed
On 13 Dec, 2020
Reviewers invited
Invitations sent on 11 Dec, 2020
Editor assigned
On 10 Dec, 2020
Submission checks complete
On 10 Dec, 2020
Editor invited
On 10 Dec, 2020
First submitted
On 08 Dec, 2020
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Subject Areas
Internal Medicine
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This preprint is under consideration at EJNMMI Research. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Original research
Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor
Kyoichi Kaira
Saitama University Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5548-7686
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 16 Dec, 2020
No community comments so far
Review #4 received
Received 10 Jan, 2021
Editorial decision: Major Revision
On 10 Jan, 2021
Review #3 received
Received 09 Jan, 2021
Reviewer #4 agreed
On 30 Dec, 2020
Reviewer #3 agreed
On 30 Dec, 2020
Review #2 received
Received 26 Dec, 2020
Review #1 received
Received 25 Dec, 2020
Reviewer #2 agreed
On 15 Dec, 2020
Reviewer #1 agreed
On 13 Dec, 2020
Reviewers invited
Invitations sent on 11 Dec, 2020
Editor assigned
On 10 Dec, 2020
Submission checks complete
On 10 Dec, 2020
Editor invited
On 10 Dec, 2020
First submitted
On 08 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
2-Deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (18F-FDG-PET) is a convenient modality to assess metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs.
Methods
A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C and β2 adrenergic receptor.
Results
High uptakes of SUVmax, SUVmean, MTV and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%) and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS of 1-2, thymic carcinoma and advanced stage, and SUVmax on 18F-FDG uptake displayed a close association with PD-L1 and PD-L2 expression, but not MTV and TLG. Multivariate analysis revealed that SUVmax was identified as an independent predictor for positive PD-L1 /PD-L2 expression. GLUT1 was clarified as a significant marker for the expression of PD-L1/PD-L2 from the biological viewpoint.
Conclusion
18F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect glucose metabolism and hypoxia in thymic tumor cells.
Figure 1
Figure 2
Figure 3