Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer
| العنوان: | Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer |
|---|---|
| المؤلفون: | Wen-Feng Zhang, Lei Wu, Hao Wu, Wei-Wei Deng, Liang Mao, Jian-Feng Liu, Zhi-Jun Sun, Lei-Lei Yang |
| المصدر: | Journal of Experimental & Clinical Cancer Research, Vol 37, Iss 1, Pp 1-8 (2018) Journal of Experimental & Clinical Cancer Research : CR |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1756-9966 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::297050b03c627bb7fd8f16e8bf3da156Test http://link.springer.com/article/10.1186/s13046-018-0713-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....297050b03c627bb7fd8f16e8bf3da156 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17569966 |
|---|