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Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 37, Iss 1, Pp 1-8 (2018), Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Background T-cell immunoglobulin mucin 3 (TIM3) is a negative immune checkpoint and plays a crucial part in tumor-induced immune suppression. However, the mechanism of TIM3 in regulating immunosuppression in head and neck squamous cell carcinoma (HNSCC) was still not quite clear. Methods We carried out the immunohistochemistry staining of HNSCC tissue microarrays. Through quantification of the histoscore, we performed the correlation analysis among the TIM3, Galectin-9, Foxp3, CD68 and CD163. The effects of TIM3 on regulatory T cells (Tregs) and macrophages were detected by utilizing the Tgfbr1/Pten 2cKO HNSCC mouse model. Flow cytometry were used to analysis the percent of Tregs, macrophages and IFN-γ. Results We demonstrated the close association among TIM3/Galectin-9 pathway, regulatory T cell marker (Foxp3) and macrophage marker (CD68, CD163) in human HNSCC. In the transgenic HNSCC mouse model, blockade of TIM3 by the anti-TIM3 monoclonal antibody induced a reduction of CD4+CD25+Foxp3+ Tregs. Meanwhile, the population of TIM3+ Tregs was also decreased. However, the population of CD206+ macrophages was not significantly declined. The increased IFN-γ production on CD8+ T cells in anti-TIM3 treatment mice showed that the antitumor immune response was enhanced through suppression of these negative immune factors. Conclusions The present study demonstrated that TIM3 was associated with the immunosuppression in HNSCC. And targeting TIM3 can enhance anti-tumor immune response by decreasing Tregs in HNSCC.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
CD8-Positive T-Lymphocytes
T-Lymphocytes, Regulatory
Mice
0302 clinical medicine
IL-2 receptor
Head and neck cancer
Hepatitis A Virus Cellular Receptor 2
Mice, Knockout
FOXP3
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunohistochemistry
medicine.anatomical_structure
Oncology
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Immunotherapy
Immune checkpoint
Signal Transduction
Regulatory T cell
chemical and pharmacologic phenomena
Tregs
lcsh:RC254-282
Immunophenotyping
03 medical and health sciences
Interferon-gamma
Immune system
otorhinolaryngologic diseases
medicine
Immune Tolerance
Animals
Humans
business.industry
Gene Expression Profiling
Research
Macrophages
medicine.disease
Head and neck squamous-cell carcinoma
Disease Models, Animal
stomatognathic diseases
030104 developmental biology
Cancer research
business
CD8
Biomarkers
Immunosuppression
Subjects
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 37
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....297050b03c627bb7fd8f16e8bf3da156