A link between the metabolic profile and T cell infiltration and function in HNSCC

Introduction In HNSCC checkpoint blockade is of limited efficacy. Therapy response depends on T cell infiltration and function, which is affected by the metabolic tumor milieu. We hypothesize that metabolic conditions impact immune infiltrate and function, thereby response to checkpoint inhibition.

Objectives We investigated the metabolic profile in tissue biopsies and interstitial fluid of tumor and corresponding mucosa in correlation to immune infiltrate, considering tumor localization and stage.

Material and methods Immune infiltration/activation were analyzed by flow cytometry, the metabolic profile by mass spectrometry.

Results Investigating central metabolites of glucose, TCA and amino acid metabolism, we show tumor-related differences in metabolite levels, impacted by stage and localization. The analysis of interstitial fluid, representing the extracellular milieu immune cells are located, revealed alterations not detected in whole tissue. Immune infiltrate was characterized by a significant decrease in T cell counts and concomitant increase in myeloid derived suppressor cells compared to mucosa. Relating metabolite abundance and T cell infiltration/activation revealed significant correlations, e.g. a negative correlation between 2-hydroxyglutarate and T cell count and a positive correlation between activation related surface markers as CD69 and glutamine levels.

Conclusion The metabolic profile, imprinted by stage and localization, correlated with T cell abundance and activation. Analysis of metabolites in the interstitial fluid provided further information on specific alterations, not observed in whole tissue. Our results provide a prospective for combinations of checkpoint blockade with anti-metabolic drugs to enhance anti-tumoral immune response in HNSCC.

Publikationsverlauf

Artikel online veröffentlicht:
24. Mai 2022