The expression of the adenosine-pathway markers CD39 and CD73 in salivary gland carcinomas harbors the potential for novel immune-checkpoint inhibition

Background: In salivary-gland-carcinomas (SGC), there is only a small fraction of entities that appears to profit from immune-checkpoint-inhibition (ICI). Recent findings connected the activation of adenosine-signaling with a tolerogenic microenvironment. Therefore, the inhibition of adenosine-pathway markers (CD39 and/or CD73) can augment ICI and/or display a novel immunotherapeutic strategy beyond ICI. Here, we assessed the immunohistochemical expression of CD39 and CD73 across a wide spectrum of SGCs. Methods In total, 114 patients with SGCs consecutively diagnosed between 2001 and 2021 were assessed for clinicopathological baseline-characteristics and underwent confirmatory histopathological review. Immunohistochemical expression-levels of CD39 and CD73 were assessed by applying the tumor-proportion-score (TPS) and the immune-proportional-score (IPS) comparable to PD-L1 expression analysis in routine clinical practice. Additionally, findings were correlated with PD-L1 expression-levels. Results The median age was 60.6 and 51.8% patients were female. The cohort covered a spectrum of eight distinct entities. Advanced-stage disease (UICC/AJCC III/IVA-IVC) at initial diagnosis was present in the majority of patients (64/114). Immunohistochemical-staining revealed positivity for CD39 and CD73 in 48.2% and 21.1% on tumor-cells (TPS ≥ 1%) as well as 46.4% and 42.9% within the immune-cell infiltrate (IPS ≥ 1%), respectively. Further comparative analyses revealed immune-cold entities such adenoidcystic-carcinoma (AdCC), immune-hot tumors such as adenocarcinoma, not otherwise specified (AC (NOS)) and entities with intermediate immunologic features such as acinic-cell-carcinoma (ACC). Conclusion Current results indicate entity-specific adenosine-signaling signatures. These findings suggest that the adenosine-pathway plays a decisive role in tumor immunity among the major spectrum of SGCs. Targeting the adenosine-pathway might pose a promising therapeutic option for selected entities.