title: Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer.
abstract: Regulatory T (Treg) cells reside in lymphoid organs and barrier tissues where they control different types of inflammatory responses. Treg cells are also found in human cancers, and studies in animal models suggest that they contribute to cancer progression. However, properties of human intratumoral Treg cells and those present in corresponding normal tissue remain largely unknown. Here, we analyzed features of Treg cells in untreated human breast carcinomas, normal mammary gland, and peripheral blood. Tumor-resident Treg cells were potently suppressive and their gene-expression pattern resembled that of normal breast tissue, but not of activated peripheral blood Treg cells. Nevertheless, a number of cytokine and chemokine receptor genes, most notably CCR8, were upregulated in tumor-resident Treg cells in comparison to normal tissue-resident ones. Our studies suggest that targeting CCR8 for the depletion of tumor-resident Treg cells might represent a promising immunotherapeutic approach for the treatment of breast cancer.
authors.affiliation: Howard Hughes Medical Institute, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: George
authors.initials: G
authors.lastname: Plitas
authors.affiliation: Howard Hughes Medical Institute, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Konopacki
authors.affiliation: Howard Hughes Medical Institute, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Kenmin
authors.initials: K
authors.lastname: Wu
authors.affiliation: Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors.forename: Paula D
authors.initials: PD
authors.lastname: Bos
authors.affiliation: Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation Barcelona 08003, Spain; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Putintseva
authors.affiliation: Central European Institute of Technology, Brno 60177, Czech Republic; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia; Pirogov Russian National Research Medical University, Moscow 117997, Russia.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Chudakov
authors.affiliation: Howard Hughes Medical Institute, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rudenska@mskcc.org.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D008875:Middle Aged; D010641:Phenotype; D054401:Receptors, CCR8 / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: C103330:CCR8 protein, human; D054401:Receptors, CCR8