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Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer

G. Plitas, C. Konopacki, K. Wu, PD. Bos, M. Morrow, EV. Putintseva, DM. Chudakov, AY. Rudensky,

. 2016 ; 45 (5) : 1122-1134.

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17031290

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.

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$a Regulatory T (Treg) cells reside in lymphoid organs and barrier tissues where they control different types of inflammatory responses. Treg cells are also found in human cancers, and studies in animal models suggest that they contribute to cancer progression. However, properties of human intratumoral Treg cells and those present in corresponding normal tissue remain largely unknown. Here, we analyzed features of Treg cells in untreated human breast carcinomas, normal mammary gland, and peripheral blood. Tumor-resident Treg cells were potently suppressive and their gene-expression pattern resembled that of normal breast tissue, but not of activated peripheral blood Treg cells. Nevertheless, a number of cytokine and chemokine receptor genes, most notably CCR8, were upregulated in tumor-resident Treg cells in comparison to normal tissue-resident ones. Our studies suggest that targeting CCR8 for the depletion of tumor-resident Treg cells might represent a promising immunotherapeutic approach for the treatment of breast cancer.
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$a Wu, Kenmin $u Howard Hughes Medical Institute, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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$a Bos, Paula D $u Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
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$a Putintseva, Ekaterina V $u Bioinformatics and Genomics Programme, Centre for Genomic Regulation Barcelona 08003, Spain; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia.
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$a Chudakov, Dmitriy M $u Central European Institute of Technology, Brno 60177, Czech Republic; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia; Pirogov Russian National Research Medical University, Moscow 117997, Russia.
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$a Rudensky, Alexander Y $u 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.
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