The expression of PD-L1 in salivary gland carcinomas

Abstract

Objective was to analyze the role of PD-L1 and its relation to demographic, patho-clinical and outcome parameters in salivary gland carcinoma (SGC) patients. Patients treated for salivary gland carcinomas between 1994 and 2010 were included. A retrospective chart review for baseline characteristics, pathohistological, clinical and outcome data was performed. Immunohistochemistry for PD-L1 was performed using tissue microarrays. PD-L1 expression was assessed in tumor cells and tumor-infiltrating immune cells (TIIC) and statistical analysis with regard to baseline and outcome data was performed. Expression of PD-L1 (by means ≥1% of the cells with PD-L1 positivity) was present in the salivary gland carcinoma cells of 17%, in the TIIC of 20% and in both tumor cells and TIIC of 10% the patients. PD-L1 expression in tumor cells and both tumor cells and TIIC was related to tumor grading (p = 0.035 and p = 0.031, respectively). A trend towards higher grading was also seen for PD-L1 expression in TIICs (p = 0.058). Patients with salivary duct carcinomas and PD-L1 expressing TIICs showed a significantly worse DFS and OS (p = 0.022 and p = 0.003, respectively), those with both tumor cells and TIIC expressing PD-L1 a significantly worse DFS (p = 0.030). PD-L1 expression is present in 17% and 20% of salivary gland carcinoma cells and TIIC. Ten percent of the patient showed a PD-L1 positivity in both tumor cells and TIIC. This is related to high tumor grading and therefore might be a negative prognostic factor.

Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

“…The clinicopathological characteristics of the investigated cohort were comparable to the results from other studies, even though the proportion of AC, NOS was slightly higher when compared to other cohorts [16]. Patients with AC, NOS presented at higher age and a higher frequency of metastatic disease is in line with previous reports [19,20].…”

“…In line with that, a majority of AC, NOS (67%) cases was scored with IC values of 2 or 3, which highlights the tumor area covered by PD-L1 positive immune cells. In the recent study from Vital et al, the authors found a higher frequency of PD-L1 + MEC compared to AC, NOS, AdCC, and ACC [16]. However, given the fact that the authors used a different antibody clone (SP142) and adapted the cutoff of 1% PD-L1 + tumor cells that had initially been reported for NSCLC and gastric cancer.…”

“…There are promising results from checkpoint inhibitor therapy in malignant salivary gland tumors, but there is limited data on PD-L1 scoring in these tumors, and no objective scoring criteria has, so far, been evaluated [13,16,17]. While most previous studies focused on the prognostic value of PD-L1 expression, the aim of the present study was to employ established predictive scoring criteria from other tumor entities for the evaluating PD-L1 expression in SGC and to identify entities among SGC that might be promising targets for immuno-oncologic treatment.…”

“…However, the cutoff for PD-L1 expression (clone 22C3) was chosen as ≥1% of a PD-L1-positive tumor or stromal cells based on studies from NSCLC and gastric cancer [14,15]. In a recent study by Vital et al applying the identical 1% cutoff for PD-L1 positivity (clone SP142), the authors identified 17% of PD-L1 positive SGC (28 of 167 cases) and 20% of tumors with PD-L1-positive infiltrating immune cells (33 of 167 cases) over all histological subgroups [16]. In a smaller cohort of 47 patients, Harada et al found PD-L1 positivity (clone name not given) in 51.1% of malignant salivary gland tumors using a cutoff of 5% tumor cells with membranous PD-L1 staining [17].…”

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment

“…Most SDC cases are microsatellite‐stable and have a low TMB 59,63,70,73,82 . There are no consistent data on PD‐L1 expression 59‐64 . A study of immune checkpoint inhibitor (pembrolizumab) treatment for advanced salivary gland carcinoma reported a 12% response rate, and another study of pembrolizumab included 1 SDC case in the cohort 109,110 .…”