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

Publication date: January 2019

Source: Oral Oncology, Volume 88

Author(s): Carla Mosconi, José Alcides Almeida de Arruda, Ana Caroline Rodrigues de Faria, Gabriella Alves Quixabeira Oliveira, Henrique Moura de Paula, Felipe Paiva Fonseca, Ricardo Alves Mesquita, Tarcília Aparecida Silva, Elismauro Francisco Mendonça, Aline Carvalho Batista

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.

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