CD103+ tissue-resident T-cells in head and neck squamous cell carcinomas of patients treated anti-PD-1 therapy

PURPOSE: Anti-PD-1 therapy is nowadays the state of the art treatment in advanced-stage head and neck squamous cell carcinoma (HNSCC), showing improved survival rates in contrast to chemotherapy, but still lacking reliable biomarkers for therapy response prediction. The aim of the study was to investigate whether specific subtypes of immune cells could predict the response to anti-PD-1 therapy. MATERIAL AND METHODS: The infiltration density of CD8+, CD69+, CD103+ and PD-1+ cells were performed in a large HNSCC cohort (n=125) and correlated with clinic-pathological data and follow-up. Additionally, the infiltration density of CD103+, CD69+ or PD-1+ lymphocytes in a cohort of advanced primary HNSCC cases treated with immune checkpoint therapy (pembrolizumab or nivolumab) during course of the disease was examined by immunohistochemistry (primary tumors n=56, paired local recurrences n=12, paired lung metastases n=5). RESULTS: In the HNSCC cohort, poorer differentiation was associated with higher infiltration density of CD8+, CD69+ and CD103+ lymphocytes (p=0.025, p=0.024, and p=0.043, respectively). Nodal-positive HNSCC showed a significantly higher infiltration density of CD103+ lymphocytes (p=0.026). There was no association between infiltration density of CD103+, CD69+ or PD-1+ cells to the response to immune checkpoint inhibition in the relatively small and heterogenous ICI therapy cohort. CONCLUSION: CD103+ tissue-resident T-cells accumulate in poorly differentiated, nodal positive tumors as well as in non-smokers in HNSCC. There was no association between infiltration density of CD103+, CD69+ or PD-1+ cells to the response to immune checkpoint inhibition in a small retrospective therapy cohort.