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

被引:79
作者
Sridharan, Vishwajith [1 ,2 ]
Gjini, Evisa [3 ]
Liao, Xiaoyun [3 ]
Chau, Nicole G. [5 ]
Haddad, Robert I. [5 ]
Severgnini, Mariano [4 ]
Hammerman, Peter [5 ]
El-Naggar, Adel [6 ]
Freeman, Gordon J. [5 ]
Hodi, F. Stephen [4 ,5 ]
Rodig, Scott J. [7 ]
Dranoff, Glenn [8 ]
Schoenfeld, Jonathan D. [1 ]
机构
[1] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA
[2] Harvard Med Sch, Harvard MIT Div Hlth Sci & Technol, Boston, MA USA
[3] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Dana Farber Canc Ctr, Ctr Immunooncol, 75 Francis St, Boston, MA 02115 USA
[5] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA
[6] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[7] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Ctr, 75 Francis St, Boston, MA 02115 USA
[8] Novartis Inst Biomed Res, Cambridge, MA USA
关键词
CELL LUNG-CANCER; METASTATIC MELANOMA; MUTATIONAL LANDSCAPE; ANTI-PD-L1; ANTIBODY; BREAST-CANCER; NECK-CANCER; BLOCKADE; IMMUNOTHERAPY; IPILIMUMAB; HEAD;
D O I
10.1158/2326-6066.CIR-16-0031
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 beta-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. (C) 2016 AACR.
引用
收藏
页码:679 / 687
页数:9
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