Loss of SHP-2 activity in CD4 + T cells promotes melanoma progression and metastasis

Tao Zhang, Wenjie Guo, Yang Yang, Wen Liu, Lele Guo, Yanhong Gu, Yongqian Shu, Lu Wang, Xuefeng Wu, Zichun Hua, Yuehai Ke, Yang Sun, Yan Shen, Qiang Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) has been reported to have both tumor-promoting and tumor-suppressing roles in tumorigenesis. However, the role of SHP-2 in tumor immunity remains unclear. Here we observed progressively lower levels of phosphorylated SHP-2 in tumor-associated CD4 + T cells during melanoma development in a murine model. Similarly, the levels of phosphorylated SHP-2 in the CD4 + T cells of human melanoma specimens revealed a decrease paralleling cancer development. The CD4 + T cell-specific deletion of SHP-2 promoted melanoma metastasis in mice. Furthermore, SHP-2 deficiency in CD4 + T cells resulted in the increased release of inflammatory cytokines, especially IL-6, and the enhanced accumulation of tumor-promoting myeloid-derived suppressor cells (MDSCs) in tumor-bearing mice. An IL-6-neutralizing antibody reduced MDSC accumulation and inhibited tumor growth in CD4 + T-cell-specific SHP-2-knockout mice. Our results suggest that SHP-2 in CD4 + T cells plays an important role in preventing melanoma progression and metastasis.

Original languageEnglish (US)
Article number2845
JournalScientific reports
Volume3
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • General

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