TY - JOUR
T1 - Immune Profiling of Adenoid Cystic Carcinoma
T2 - PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes
AU - Sridharan, Vishwajith
AU - Gjini, Evisa
AU - Liao, Xiaoyun
AU - Chau, Nicole G.
AU - Haddad, Robert I.
AU - Severgnini, Mariano
AU - Hammerman, Peter
AU - El-Naggar, Adel
AU - Freeman, Gordon J.
AU - Hodi, F. Stephen
AU - Rodig, Scott J.
AU - Dranoff, Glenn
AU - Schoenfeld, Jonathan D.
N1 - Publisher Copyright:
©2016 American Association for Cancer Research.
PY - 2016
Y1 - 2016
N2 - 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 b-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.
AB - 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 b-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.
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U2 - 10.1158/2326-6066.CIR-16-0031
DO - 10.1158/2326-6066.CIR-16-0031
M3 - Article
C2 - 27312343
AN - SCOPUS:84985947477
SN - 2326-6066
VL - 4
SP - 679
EP - 687
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 8
ER -