Immunological and metabolic characterization in HNSCC

The HNSCC is the 6th most prevalent malignant disease worldwide. The current treatment includes surgery, and radio(chemo)therapy and antibody therapy. 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 in different regions of HNSCC. We focused on regulatory T cells, antigen presenting cells, and the expression of costimulatory as well as inhibitory molecules on tumor infiltrating immune cells. We also investigated alterations of tumor metabolism in HNSCC. Our study aims to find a link between a diminished T cell functionality and changes in tumor metabolism. We analyzed biopsies from different tumor regions and corresponding healthy mucosa of 50 patients by flow cytometry. Metabolic analysis were performed by mass spectrometry.

Results Comparing tumor tissue with corresponding healthy mucosa, we observed a significant decrease in the number of intra-tumoral CD4+ as well as CD8+ T cells while different types of myeloid cells were massively increased. The comparison of the immune cell populations in different tumor regions revealed no significant differences. By investigation of the tumor metabolism, we could show increased lactate levels in tumor tissue. Changes in amino acid metabolism and the citric acid cycle could be observed.

Conclusion We could clearly show that HNSCC is characterized by a massive infiltration with neutrophilic granulocytes and low numbers of lymphocytes associated with high lactate levels. These findings support a possible prospective combination of checkpoint therapy with anti-metabolic drugs in HNSCC

Publication History

Article published online:
10 June 2020