Validation and characterisation of prognostically significant PD-L1+ immune cells in HPV+ oropharyngeal squamous cell carcinoma

We previously showed in human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) that the presence of intratumoral (IT) PD-L1 immune cells (ICs) or CD8 infiltrating ICs are of prognostic value. Here we report the prognostic significance of these immune biomarkers in an independent validation cohort of 177 HPV+OPSCC patients. IT and stromal (S) localisation of PD-L1 and CD8 ICs were scored. High abundance (≥5%) of PD-L1 IT ICs was found in 51/167 patients (30.5%) and was associated with improved overall survival (OS) (HR, 0.21; 95% CI, 0.05–0.91; P = 0. 012) validating our previous results. High abundance (≥30%) of CD8 IT or S ICs, found in 77/167 patients (46.1%) provided a HR of 0.45 for OS however the confidence interval was wide (95% CI 0.16–1.25, p = 0.105). Multiplex immunohistochemistry revealed CD68 macrophages and CD3CD8 T cells to be the most common ICs expressing PD-L1. Gene expression analysis showed tumors with high abundance of PD-L1 IT ICs exhibit gene signatures associated with responses to PD1 or PD-L1 inhibitors pembrolizumab and atezolizumab. These data support the role of immune biomarkers such as PD-L1 ICs to identify subgroups of HPV+OPSCC patients with an excellent outcome that may be suitable for trials evaluating de-intensification of therapy