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 CD3 ⁺ CD8 ⁺ 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.
Competing Interests: Declaration of Competing Interest The authors make the following declaration of competing interests, all outside the submitted work: RY - institutional research funding, Roche; SP - advisory boards, MSD, Merck; honoraria, Celgene; DU - lecture fees, Bristol Myers Squibb (BMS); travel fees and lecture fees, Merck Sharp & Dohme (MSD); travel fees and lecture fees, Roche; CC - advisory boards, MSD (no honorarium); travel, accommodations and expenses, Pfizer, MSD; PN – honoraria, BMS; institutional research funding, BMS, Roche Genentech, Celgene-Juno, Advaxis, Compugen and Allergan; DR - institutional research funding, MSD, Merck, BMS, GSK, Roche, Regeneron, Amgen; Travel, MSD; advisory boards/trial steering committees (all uncompensated), MSD, Merck, BMS, GSK, Regeneron, Merck; BS – honoraria, BMS, AstraZeneca (Inst); consulting or advisory role, BMS, MSD, AstraZeneca, Pfizer, Genentech, Eisai; institutional research funding, Pfizer, Roche; royalties from Veristrat (Biodesix); UpToDate; travel, accommodation and expenses, AstraZeneca, Roche, Merck, BMS, Novartis. All remaining authors have declared no conflicts of interest.
(Copyright © 2019. Published by Elsevier Ltd.)