Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer
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...
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0713-7 |
| _version_ | 1831840508982329344 |
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| author | Jian-Feng Liu Lei Wu Lei-Lei Yang Wei-Wei Deng Liang Mao Hao Wu Wen-Feng Zhang Zhi-Jun Sun |
| author_facet | Jian-Feng Liu Lei Wu Lei-Lei Yang Wei-Wei Deng Liang Mao Hao Wu Wen-Feng Zhang Zhi-Jun Sun |
| author_sort | Jian-Feng Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T06:12:07Z |
| format | Article |
| id | doaj.art-74634cb344c64111bc5078e3063ccb70 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-23T06:12:07Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-74634cb344c64111bc5078e3063ccb702022-12-21T17:57:25ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-03-013711810.1186/s13046-018-0713-7Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancerJian-Feng Liu0Lei Wu1Lei-Lei Yang2Wei-Wei Deng3Liang Mao4Hao Wu5Wen-Feng Zhang6Zhi-Jun Sun7The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityDepartment of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityAbstract 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.http://link.springer.com/article/10.1186/s13046-018-0713-7Head and neck cancerImmunosuppressionImmunotherapyImmune checkpointTregsMacrophages |
| spellingShingle | Jian-Feng Liu Lei Wu Lei-Lei Yang Wei-Wei Deng Liang Mao Hao Wu Wen-Feng Zhang Zhi-Jun Sun Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer Journal of Experimental & Clinical Cancer Research Head and neck cancer Immunosuppression Immunotherapy Immune checkpoint Tregs Macrophages |
| title | Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer |
| title_full | Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer |
| title_fullStr | Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer |
| title_full_unstemmed | Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer |
| title_short | Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer |
| title_sort | blockade of tim3 relieves immunosuppression through reducing regulatory t cells in head and neck cancer |
| topic | Head and neck cancer Immunosuppression Immunotherapy Immune checkpoint Tregs Macrophages |
| url | http://link.springer.com/article/10.1186/s13046-018-0713-7 |
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