Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer

• Published in: Immunity (Cambridge, Mass.) Vol. 45; no. 5; pp. 1122 - 1134
• Main Authors: Plitas, George, Konopacki, Catherine, Wu, Kenmin, Bos, Paula D., Morrow, Monica, Putintseva, Ekaterina V., Chudakov, Dmitriy M., Rudensky, Alexander Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2016; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Breast cancer; Breast Neoplasms - immunology; Cell Separation; Chemokines; Experiments; Female; Flow Cytometry; Gene expression; Gene Expression Profiling; Humans; Lymphocytes; Lymphocytes, Tumor-Infiltrating; Medical prognosis; Medical research; Metastasis; Middle Aged; Phenotype; Receptors, CCR8 - biosynthesis; Receptors, CCR8 - immunology; Statistical analysis; T-Lymphocytes, Regulatory - immunology; Transcriptome; Tumors; Young Adult
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.10.032

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. [Display omitted] •RNA-seq analysis details the Treg cell phenotype in primary human breast carcinomas•Tumor-resident and normal tissue Treg cells exhibit similar features•Chemokine receptor CCR8 is highly expressed by Treg cells in human tumors•High CCR8 to Foxp3 mRNA ratio correlates with poor prognosis in breast cancer Treg cells are associated with poor prognosis in human cancers. Plitas et al. (2016) identify distinct and shared features of Treg cells in malignant and normal human breast tissue including tumor-specific Treg cell expression of chemokine receptor CCR8, providing means for targeted depletion of tumor-resident Treg cells as an immunotherapeutic strategy.