Inhibition of SRC family kinases reduces myeloid-derived suppressor cells in head and neck cancer

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• 作者：Liang Mao ; Wei-Wei Deng ; Guang-Tao Yu ; Lin-Lin Bu ; Jian-Feng Liu ; Si-Rui Ma ; Lei Wu ; Ashok B. Kulkarni ; Wen-Feng Zhang and Zhi-Jun Sun
• 刊名：International Journal of Cancer
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：140
• 期：5
• 页码：1173-1185
• 全文大小：1052K
• ISSN：1097-0215

文摘

SRC family kinases (SFKs), a group of nonreceptor tyrosine kinases, modulate multiple cellular functions, such as cell proliferation, differentiation and metabolism. SFKs display aberrant activity in progressive stages of human cancers. However, the precise role of SFKs in the head and neck squamous cell carcinoma (HNSCC) signaling network is far from clear. In this study, we found that the inhibition of SFKs activity by dasatinib effectively reduced the tumor size and population of MDSCs in the HNSCC mouse model. Molecular analysis indicates that phosphorylation of LYN, rather than SRC, was inhibited by dasatinib treatment. Next, we analyzed LYN expression by immunostaining and found that it was overexpressed in the human HNSCC specimens. Moreover, LYN expression in stromal cells positively correlated with myeloid-derived suppressor cells (MDSCs) makers CD11b and CD33 in human HNSCC. The dual positive expression of LYN in epithelial and stromal cells (EPI⁺ SRT⁺) was associated with unfavorable overall survival of HNSCC patients. These findings indicate that SFKs may be a potential target for an effective immunotherapy of HNSCC by decreasing MDSCs and moreover, LYN will have an impact on such therapeutic strategy.