Specific recruitment of γδ regulatory T cells in human breast cancer

Jian Ye, Chunling Ma, Fang Wang, Eddy C. Hsueh, Karoly Toth, Yi Huang, Wei Mo, Shuai Liu, Bing Han, Mark A. Varvares, Daniel F. Hoft, Guangyong Peng

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Understanding the role of different subtypes of tumor-infiltrating lymphocytes (TIL) in the immunosuppressive tumor microenvironment is essential for improving cancer treatment. Enriched γδ1 T-cell populations in TILs suppress T-cell responses and dendritic cell maturation in breast cancer, where their presence is correlated negatively with clinical outcomes. However, mechanism(s) that explain the increase in this class of regulatory T cells (γδ Treg) in patients with breast cancer have yet to be elucidated. In this study, we show that IP-10 secreted by breast cancer cells attracted γδ Tregs. Using neutralizing antibodies against chemokines secreted by breast cancer cells, we found that IP-10 was the only functional chemokine that causes γδ Tregs to migrate toward breast cancer cells. In a humanized NOD-scid IL-2Rγnull (NSG) mouse model, human breast cancer cells attracted γδ Tregs as revealed by a live cell imaging system. IP-10 neutralization in vivo inhibited migration and trafficking of γδ Tregs into breast tumor sites, enhancing tumor immunity mediated by tumor-specific T cells. Together, our studies show how γδ Tregs accumulate in breast tumors, providing a rationale for their immunologic targeting to relieve immunosuppression in the tumor microenvironment.

Original languageEnglish
Pages (from-to)6137-6148
Number of pages12
JournalCancer research
Issue number20
StatePublished - Oct 15 2013


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