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Highlights • PD-L1 and CD8 expression were significantly higher in p16-positive OPSCC patients. • Higher PD-L1 expression in TC and IC showed better survival than that of lower. • Higher CD8 expression showed better survival than that of lower. • PD-L1 expression in TC and IC can be useful for predicting the response of RT. Abstract Background and purpose To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). Material and methods We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy. Results Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1–3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0–2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0–2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors. Conclusions In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy. [ABSTRACT FROM AUTHOR]