Prognostic impact of CD8-positive tumour-infiltrating lymphocytes and PD-L1 expression in salivary gland cancer
Nikolina Kesar, Ria Winkelmann, Julius Oppermann, Shahram Ghanaati, Daniel Martin, Thomas Neumayer, Sven Balster, Claus Rödel, Franz Rödel, Jens von der Grün, Panagiotis Balermpas
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.