Prognostic impact of CD8-positive tumour-infiltrating lymphocytes and PD-L1 expression in salivary gland cancer

Abstract

Aim of the study was to evaluate the prognostic impact of CD8-positive (CD8+) tumour-infiltrating lymphocytes (TILs) and PD-L1 expression on the outcome of patients with malignant salivary gland neoplasms. Formalin-fixed, paraffin-embedded tissue samples and clinicopathological data from patients treated for salivary gland carcinoma in a head and neck cancer centre were retrospectively retrieved. Immunohistochemical staining was applied on sections of 84 specimens of 12 different histological subtypes. Both CD8 and PD-L1 expression were rated by semi-automated cell counts by a digital image analysis programme. Survival analyses were performed by the log-rank test on the univariate level, and the Cox model was applied on the multivariate level. Associations between immunological markers and clinicopathological variables were estimated by the Pearson chi-squared test. Additionally, PD-1 was estimated as an exhaustion marker of CD8+ TILs. Patients exceeding a tumour proportion score ≥5% regarding PD-L1 expression demonstrated a significantly decreased survival, as did individuals with an overall high CD8+ cell density. Particularly, high CD8+ cell counts in the invasive front of the respective tumour tissue significantly coincided with a poor outcome. Also, high numbers of CD8+ TILs significantly matched with a high quantity of PD-1+ TILs. CD8+ TILs abundance in the peritumoural microenvironment correlates with impaired outcome of patients with salivary gland carcinoma. The simultaneous negative prognostic impact of PD-L1 expression and presence of PD-1+ TILs advocates an immune checkpoint-controlled mechanism of CD8+ TILs exhaustion for these tumours and paves the way for future treatment strategies.