title: Specific recruitment of γδ regulatory T cells in human breast cancer.
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.
authors: Authors' Affiliations: Division of Infectious Diseases, Allergy & Immunology, Department of Internal Medicine, Departments of Surgery, Molecular Microbiology and Immunology, and Otolaryngology-Head and Neck Surgery, Saint Louis University School of Medicine, Saint Louis, Missouri; Department of Immunology and Microbiology, Shandong Medical College, Linyi; and Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors: Jian
authors: J
authors: Ye
authors: Chunling
authors: C
authors: Ma
authors: Fang
authors: F
authors: Wang
authors: Eddy C
authors: EC
authors: Hsueh
authors: Karoly
authors: K
authors: Toth
authors: Yi
authors: Y
authors: Huang
authors: Wei
authors: W
authors: Mo
authors: Shuai
authors: S
authors: Liu
authors: Bing
authors: B
authors: Han
authors: Mark A
authors: MA
authors: Varvares
authors: Daniel F
authors: DF
authors: Hoft
authors: Guangyong
authors: G
authors: Peng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta
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