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PD-1 blockade attenuates immunosuppressive myeloid cells due to inhibition of CD47/SIRPα axis in HPV negative head and neck squamous cell carcinoma
- Source :
- Oncotarget
- Publication Year :
- 2015
- Publisher :
- Impact Journals, LLC, 2015.
-
Abstract
- Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) play key roles in the tumor immune suppressive network and tumor progression. However, precise roles of programmed death-1 (PD-1) in immunological functions of MDSCs and TAMs in head and neck squamous cell carcinoma (HNSCC) have not been clearly elucidated. In the present study, we show that PD-1 and PD-L1 levels were significantly higher in human HNSCC specimen than in normal oral mucosa. MDSCs and TAMs were characterized in mice and human HNSCC specimen, correlated well with PD-1 and PD-L1 expression. αPD-1 treatment was well tolerated and significantly reduced tumor growth in the HNSCC mouse model along with significant reduction in MDSCs and TAMs in immune organs and tumors. Molecular analysis suggests a reduction in the CD47/SIRPα pathway by PD-1 blockade, which regulates MDSCs, TAMs, dendritic cell as well as effector T cells. Hence, these data identify that PD-1/PD-L1 axis is significantly increased in human and mouse HNSCC. Adoptive αPD-1 immunotherapy may provide a novel therapeutic approach to modulate the micro- and macro- environment in HNSCC.
- Subjects :
- medicine.medical_treatment
Blotting, Western
Programmed Cell Death 1 Receptor
Receptor, Transforming Growth Factor-beta Type I
CD47 Antigen
Protein Serine-Threonine Kinases
Biology
HNSCC
B7-H1 Antigen
myeloid-derived suppressor cell
Immune system
stomatognathic system
Cell Line, Tumor
PD-1
medicine
Animals
Humans
Myeloid Cells
Receptors, Immunologic
tumor associated macrophagy
Papillomaviridae
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
Macrophages
CD47
PTEN Phosphohydrolase
Antibodies, Monoclonal
Immunotherapy
Dendritic cell
medicine.disease
Antigens, Differentiation
Immunohistochemistry
Head and neck squamous-cell carcinoma
Gene Expression Regulation, Neoplastic
stomatognathic diseases
Oncology
Head and Neck Neoplasms
Tumor progression
Immunology
Myeloid-derived Suppressor Cell
Cancer research
RNA Interference
Signal transduction
Receptors, Transforming Growth Factor beta
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....af64e5fc7a45af267be48589d6e057fd