Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer

Overview

Journal Cancer Res

Specialty Oncology

Date 2013 Aug 21

PMID 23959855

Citations 62

Authors

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

Affiliations

Soon will be listed here.

Abstract

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-2Rγ(null) (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.

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