Immune microenvironment and evasion mechanisms in adenoid cystic carcinomas of salivary glands

Abstract

Objectives: The objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands.

Materials and methods: Thirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8⁺ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion.

Results: ACC showed low CD8⁺, GrB⁺ TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8⁺ TIL density presented greater recurrence rates.

Conclusion: Our findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.

Keywords: Adenoid cystic carcinoma; Head and neck cancer; Immunogenicity; Immunohistochemical; Neoplasm; Oral cancer; Salivary gland; Tumor escape.