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DOI: 10.1055/s-0041-1727903
Effects of 2-Hydroxyglutarate on immune cell composition, Tumor metabolism and prognosis in Head and Neck Squamous Cell Carcinoma
The HNSCC is the 6th most prevalent malignant disease worldwide. Immune cell infiltration is one important determinant of patient survival. Immunotherapy with checkpoint inhibitors gained growing interest in tumor therapy and immune cell infiltration may play a role for successful therapy. The focus was to investigate the heterogeneity of immune cell infiltration and alterations in tumor metabolism in HNSCC.
In the study, we established a connection of the decreased functionality of T cells and alterations in tumor metabolism. We analyzed tumor tissue and corresponding healthy mucosa of more than 60 patients with HNSCC by flow cytometry and metabolic measurements.
We could show significantly increased concentrations of 2-Hydroxyglutarate (2-HG) in tumor tissue in comparison to healthy mucosa. There was also a difference depending on the tumor localization. Especially in oropharynx and in larynx, significantly increased 2-HG level could be measured. In OSCC increased level could be measured, but without significance. There was no difference between 2-HG level in hypopharynx and healthy mucosa. Furthermore, by Floy cytometry we could show a decreased infiltration by CD4+ and CD8+ T cells. Interestingly, there was a negative correlation between increased 2-HG level and decreased CD8+ T cell infiltration in HNSCC. There was no correlation between increased infiltration by monocytic cells and increased 2-HG level.
We could show significantly increased level of the oncometabolite 2-HG in HNSCC and there was a difference depending on tumor localization. Furthermore, there was a negative correlation between a decreased infiltration by CD8+ T cells and increased 2-HG levels. The results support a possible combination of a checkpointtherapy with an antimetabolic therapy.
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Conflict of interest
Der Erstautor gibt keinen Interessenskonflikt an.
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Publication History
Article published online:
13 May 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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