Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes

Cancer Immunol Res. 2016 Aug;4(8):679-87. doi: 10.1158/2326-6066.CIR-16-0031. Epub 2016 Jun 16.


Adenoid cystic carcinoma (ACC) is among the most lethal salivary gland tumors, with no treatments for metastatic disease that prolong survival. We examined tissue from 28 primary and metastatic ACC deposits obtained from 21 patients for infiltrating immune cells and PD-L1/PD-L2 expression and determined mRNA profiles of over 1,400 oncogenic and immune-related genes. We also assessed the effect of chemoradiation on immune mediators in a patient who had serial biopsies available. Most tumors expressed PD-L2 but had few infiltrating immune cells. Lack of immune-cell infiltrate was associated with expression of genes in the β-catenin/Wnt and PI3K pathways. Additionally, certain transcripts linked to growth and invasion were differentially expressed among primary and metastatic deposits. Chemoradiation appeared to increase CD8(+) effector T cells, decrease regulatory T cells, and promote a systemic humoral response. These data suggest a potential role for PD-L2 inhibition and immune modulation as treatment for patients with ACC. Cancer Immunol Res; 4(8); 679-87. ©2016 AACR.

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / immunology*
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Adenoid Cystic / therapy
  • Chemoradiotherapy
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Neoplasm Metastasis
  • Programmed Cell Death 1 Ligand 2 Protein / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / immunology
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology


  • B7-H1 Antigen
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein