HLA Class II tetramers reveal tissue-specific regulatory T cells that suppressT-cell responses in breast carcinoma patients.

摘要

Regulatory T cells (Tregs) play an important role in controlling antitumor T-cellresponses and hence represent a considerable obstacle for cancer immunotherapy.The abundance of specific Treg populations in cancer patients has been poorlyanalyzed so far. Here, we demonstrate that in breast cancer patients, Tregs oftencontrol spontaneous effector memory T-cell responses against mammaglobin, acommon breast tissue-associated antigen that is overexpressed by breastcarcinoma. Using functional assays, we identified a HLA-DRB1*04:01- andHLA-DRB1*07:01-restricted epitope of mammaglobin (mam34-48) that was frequentlyrecognized by Tregs isolated from breast cancer patients. Using mam34-48-labeled HLA Class II tetramers, we quantified mammaglobin-specific Tregs and CD4(+)conventional T (Tcon) cells in breast carcinoma patients as well as in healthyindividuals. Both mammaglobin-specific Tregs and Tcon cells were expanded inbreast cancer patients, each constituting approximately 0.2% of their respective cell subpopulations. Conversely, mammaglobin-specific Tregs and CD4(+) Tcon cellswere rare in healthy individuals (0.07%). Thus, we provide here for the firsttime evidence supporting the expansion of breast tissue-specific Tregs and CD4(+)Tcon cells in breast cancer patients. In addition, we substantiate the potential implications of breast tissue-specific Tregs in the suppression of antitumorimmune responses in breast cancer patients. The HLA Class II tetramers used inthis study may constitute a valuable tool to elucidate the role ofantigen-specific Tregs in breast cancer immunity and to monitor breastcancer-specific CD4(+) T cells.