A retrospective analysis of tumor infiltrating lymphocytes in head and neck squamous cell carcinoma patients treated with nivolumab

Nivolumab, an immune checkpoint inhibitor is the first-line therapy for platinum-resistant recurrent/metastatic head and neck cancer, and highly effective for some patients. However, no factors have been identified that could predict response or prognosis after nivolumab administration. We retrospectively investigated the association between tumor infiltrating lymphocytes (TILs) of initial pathology and prognosis in patients treated with nivolumab. Twenty-eight patients with human papilloma virus and Epstein–Barr virus unrelated head and neck squamous cell carcinoma were enrolled. CD8(+)cells, FoxP3(+)cells and FoxP3(−)CD4(+)cells in the tumoral and peritumoral stromal area and PD-L1 were measured. In result, FoxP3(−)CD4(+)TIL, FoxP3(+)TIL, and CD8(+)TIL were not correlated with survival in either intratumoral and stromal area. In univariate analysis, objective response was significant prognostic factor both in progression-free survival and overall survival (p = 0.01, 0.006, respectively). PD-L1 was also significant prognostic factor both in progression-free survival and overall survival (p = 0.01, 0.01, respectively). ECOG Performance status was a significant prognostic factor in overall survival (p = 0.0009). In the combined analysis of stromal CD8(+)TIL and PD-L1, PD-L1 positive with high stromal CD8(+)TIL subgroups had a better prognosis than PD-L1 negative with low stromal CD8(+)TIL subgroups in progression-free survival (p = 0.006). Although these results require a further investigation, PD-L1 and ECOG Performance status and the combination of stromal CD8(+)TIL and PD-L1 positivity have potential as useful prognostic markers in patients of virus unrelated head and neck squamous cell carcinoma treated with nivolumab.