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STAT3 Induces Immunosuppression by Upregulating PD-1/PD-L1 in HNSCC
- Source :
- Journal of Dental Research. 96:1027-1034
- Publication Year :
- 2017
- Publisher :
- SAGE Publications, 2017.
-
Abstract
- Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections. PD-1/PD-L1 overexpression was found to be significantly associated with p-STAT3 in human and mouse HNSCC. Targeting STAT3 by a small molecule effectively inhibited the expression of PD-L1 in the CAL27 cell line. Furthermore, we found that blockade of STAT3 signaling downregulated PD-1/PD-L1 in a Tgfbr1/Pten 2cKO HNSCC mouse model. These findings suggest that STAT3 signaling plays an important role in PD-1/PD-L1 regulation and the antitumor immune response of HNSCC.
- Subjects :
- STAT3 Transcription Factor
Transcriptional Activation
0301 basic medicine
medicine.medical_treatment
Blotting, Western
Biology
Mice
03 medical and health sciences
0302 clinical medicine
PD-L1
medicine
Animals
Humans
PTEN
STAT3
General Dentistry
Cells, Cultured
Head and neck cancer
Research Reports
Immunotherapy
Flow Cytometry
Programmed Cell Death 1 Ligand 2 Protein
medicine.disease
Immunohistochemistry
Head and neck squamous-cell carcinoma
Immune checkpoint
Up-Regulation
stomatognathic diseases
030104 developmental biology
Cytokine
Head and Neck Neoplasms
Tissue Array Analysis
030220 oncology & carcinogenesis
Carcinoma, Squamous Cell
biology.protein
Cancer research
Signal Transduction
Subjects
Details
- ISSN :
- 15440591 and 00220345
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Journal of Dental Research
- Accession number :
- edsair.doi.dedup.....567a7d26516b9cb45f9ab2917dcc0d04