Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes.
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.
Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts.
Vishwajith
V
Sridharan
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Evisa
E
Gjini
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Xiaoyun
X
Liao
Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Nicole G
NG
Chau
Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Robert I
RI
Haddad
Center for Immuno-Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Mariano
M
Severgnini
Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Peter
P
Hammerman
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Adel
A
El-Naggar
Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Gordon J
GJ
Freeman
Center for Immuno-Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts. Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
F Stephen
FS
Hodi
Department of Pathology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts.
Scott J
SJ
Rodig
Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.
Glenn
G
Dranoff
Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, Massachusetts. jdschoenfeld@partners.org.
Jonathan D
JD
Schoenfeld
D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D009362:Neoplasm Metastasis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000276:immunology; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
D060890:B7-H1 Antigen; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein