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

Abstract

Background: Malignant neoplasms of the salivary glands are rare, and therapeutic options are limited. Results from recently published studies indicate a possible use for checkpoint inhibition in a subset of patients, but there are no established criteria for programme cell death ligand 1 (PD-L1) scoring in salivary gland carcinomas (SGCs). Methods: In this retrospective study, we present a cohort of 94 SGC patients with full clinical follow-up. We included 41 adenoid cystic carcinomas (AdCC), 21 mucoepidermoid carcinomas (MEC), 16 acinic cell carcinomas (ACC), 12 adenocarcinomas, not otherwise specified (AC, NOS), 2 epithelial-myoepithelial carcinomas (EMC), one salivary duct carcinoma (SDC), and one carcinoma ex pleomorphic adenoma (CA ex PA). Subsequent histopathological analysis was performed with special emphasis on the composition of the immune cell infiltrate (B-/T-lymphocytes). We assessed PD-L1 (SP263) on full slides by established scoring criteria: tumor proportion score (TPS), combined positivity score (CPS) and immune cell (IC) score. Results: We identified significantly elevated CD3+, TP, CP, and IC scores in AC, NOS compared to AdCC, MEC, and ACC. CPS correlated with node-positive disease. Moreover, AC, NOS displayed IC scores of 2 or 3 in the majority (67%) of cases (p = 0.0031), and was associated with poor prognosis regarding progression-free (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001). CPS correlated with strong nuclear or null p53 staining in AC, NOS but not in other SGCs. Long-lasting partial remission could be achieved in one AC, NOS patient who received Pembrolizumab as third-line therapy. Conclusions: The current study is the first to investigate the use of established scoring criteria for PD-L1 expression in malignant salivary gland tumors. Our findings identify unique characteristics for AC, NOS among the family of SGCs, as it is associated with poor prognosis and might represent a valuable target for immune checkpoint inhibition.

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

“…Moreover, SIRPα + , CD8 + , and FOXP3 + cells were counted per high power field in five dependent fields for each case. This process was based on previous studies, with modifications 32 , 33 , 49 – 51 . Statistically, the median numbers of SIRPα + , CD8 + , and FOXP3 + cells were determined as the cut-off points.…”

Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands

“…In a study by Vital et al, where 1% cutoff for PD-L1 (clone SP142) positivity was applied, the authors identified 13% of PD-L1 positive AciCCs and 20% of tumours with PD-L1 positive infiltrating immune cells [ 29 ]. Witte et al evaluated PD-L1 (clone SP263) expression in 16 AciCCs and described a median TPS of 1% and CPS of 3.5 in AciCCs, which was low compared to other salivary gland carcinomas PD-L1 [ 27 ]. The present study evaluating a cohort of 36 AciCCs observed comparable results of PD-L1 expression with PD-L1 28-8 clone.…”

“…These results are in line with other studies examining PD-L1 expression in mixed cohorts of salivary gland carcinomas. Witte et al reported a significant association between CPS and lymph node metastasis in salivary gland carcinomas [ 27 ] and Vital et al reported that PD-L1 expression in tumour cells and TILs in salivary gland carcinomas were related to higher tumour grading [ 29 ]. Higashino et al found, that PD-L1 expression in parotid carcinomas was associated with a higher-stage, higher-grade and node positive cases [ 48 ].…”

“…However, AciCCs constituted only minor subgroups in these cohorts with mixed histological cancer types, and the entity-specific prognostic role of TILs has been so far limited to adenoid cystic carcinoma [ 23 , 24 ]. Similar to the presence of TILs, the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) has been reported to be of unfavourable prognostic significance in cohorts of mixed salivary gland cancers [ 22 , 25 , 26 , 27 ], as well as in salivary duct cancer [ 13 , 28 , 29 ]. In general, expression of PD-L1 is correlated with tumour response to immune checkpoint inhibition, but the applied immunohistochemical antibodies, scoring systems and cut-offs for positivity vary greatly.…”

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response

“…IC-Score % [inflammatory cell score (stained inflammatory cells/tumour surface)] 4. CPS (combined positivity score [(stained tumour cells + stained mononuclear immune cells)/tumour cells)] ( 21 – 23 ). Although the tumour showed a moderate baseline infiltration of CD8+ cytotoxic T-cells (intratumoral CD8+ before pembrolizumab: 756 CD8+ T-cells per mm2) and PD-L1 expression on tumour (TPS 55%, CPS 70) and immune cells (IC-Score 15%), Pembrolizumab treatment led to a significant increase of CD8 infiltration with a very strong increase of intraepithelial localized CD8+ cytotoxic T-cells (intratumoral: 2221 CD8+ T-cells per mm2) and a strong upregulation of PD-L1 expression on tumour cells (TPS 100%, CPS 100) as well as on tumour infiltrating immune cells (IC-Score 40%; Figures 3A, B ) .…”