Tissue-resident memory CD8 T cells as a potential target for immune checkpoint inhibitors in head and neck squamous cell carcinoma

Introduction Response rate to anti-PD-1 immune checkpoint inhibition (ICI) is moderate in head and neck squamous cell carcinoma (HNSCC) and it remains unclear which cells exactly cause tumor inhibition. In this context CD103+ tissue-resident memory CD8 T cells (T_rm) might play a relevant role. The aim of this work is to characterize T_rm  in HNSCC and to investigate their impact on the outcome of anti-PD-1 ICI in HNSCC.

Methods T_rm  were analyzed by flow cytometry in tissue samples from 13 HNSCC patients. Immunohistochemistry (IHC) was performed to quantify CD103+ and CD8+ cells in tumor tissue from a retrospective cohort of 20 HNSCC patients who had received anti-PD-1 ICI.

Results T_rm could be detected by flow cytometry in tumor tissue of all HNSCC patients (proportion among CD3+ CD8+ T lymphocytes mean±SD: 34.4% ± 19.1%), but not in peripheral blood. PD-1 expression was significantly higher in T_rm  compared to CD103neg cytotoxic T lymphocytes (p<0.0001). CD103+ cells could also be detected by IHC in all patients. The anti-PD-1 ICI cohort was divided into the groups CD103high and CD103low as wells as CD8high and CD8low based on the median number of cells detected. For each staining, there were no differences between these groups in terms of overall survival and progression-free survival.

Conclusions T_rm  can be detected in HNSCC where they represent a significant population of CD8+ T lymphocytes. They express PD-1 at high levels and are therefore a potential target for anti-PD-1 ICI. However, the analyses to this point did not show any impact of the number of CD103+ and CD8+ cells in the tumor tissue on the outcome of PD-1 ICI in HNSCC.

Publication History

Article published online:
12 May 2023