Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer.

Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer.
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Liu JF, Wu L, Yang LL, Deng WW, Mao L, Wu H, Zhang WF, Sun ZJ,


Liu JF, Wu L, Yang LL, Deng WW, Mao L, Wu H, Zhang WF, Sun ZJ, (click to view)

Liu JF, Wu L, Yang LL, Deng WW, Mao L, Wu H, Zhang WF, Sun ZJ,

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Journal of experimental & clinical cancer research : CR 2018 03 0537(1) 44 doi 10.1186/s13046-018-0713-7

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 CD4CD25Foxp3Tregs. Meanwhile, the population of TIM3Tregs was also decreased. However, the population of CD206macrophages was not significantly declined. The increased IFN-γ production on CD8T 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.

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