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

Oral Oncol. 2019 Jan:88:95-101. doi: 10.1016/j.oraloncology.2018.11.028. Epub 2018 Nov 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen / metabolism
  • Carcinoma, Adenoid Cystic / immunology*
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Adenoid Cystic / surgery
  • Cross-Sectional Studies
  • Dendritic Cells / metabolism
  • Female
  • Follow-Up Studies
  • HLA-G Antigens / metabolism
  • Humans
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Retrospective Studies
  • Salivary Gland Neoplasms / immunology*
  • Salivary Gland Neoplasms / pathology
  • Salivary Gland Neoplasms / surgery
  • Tumor Escape / immunology*
  • Tumor Microenvironment / immunology*
  • Young Adult


  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HLA-G Antigens
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein