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1.  B cell-regulated immune responses in tumor models and cancer patients 
Oncoimmunology  2013;2(7):e25443.
The essential role played by T cells in anticancer immunity is widely accepted. The immunosuppressive functions of regulatory T cells are central for tumor progression and have been endowed with a robust predictive value. Increasing evidence indicates that also B cells have a crucial part in the regulation of T-cell responses against tumors. Although experiments reporting the production of natural antitumor antibodies and the induction of cytotoxic immune responses have revealed a tumor-protective function for B cells, other findings suggest that B cells may also exert tumor-promoting functions, resulting in a controversial picture. Here, we review recent evidence on the interactions between B and T cells in murine models and cancer patients and their implications for cancer immunology.
PMCID: PMC3782133  PMID: 24073382
antitumor immunity; B cells; regulatory B cells; T cells; Tregs; tumor-specific immune responses
2.  HLA Class II tetramers reveal tissue-specific regulatory T cells that suppress T-cell responses in breast carcinoma patients 
Oncoimmunology  2013;2(6):e24962.
Regulatory T cells (Tregs) play an important role in controlling antitumor T-cell responses and hence represent a considerable obstacle for cancer immunotherapy. The abundance of specific Treg populations in cancer patients has been poorly analyzed so far. Here, we demonstrate that in breast cancer patients, Tregs often control spontaneous effector memory T-cell responses against mammaglobin, a common breast tissue-associated antigen that is overexpressed by breast carcinoma. Using functional assays, we identified a HLA-DRB1*04:01- and HLA-DRB1*07:01-restricted epitope of mammaglobin (mam34–48) that was frequently recognized 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 healthy individuals. Both mammaglobin-specific Tregs and Tcon cells were expanded in breast cancer patients, each constituting approximately 0.2% of their respective cell subpopulations. Conversely, mammaglobin-specific Tregs and CD4+ Tcon cells were rare in healthy individuals (0.07%). Thus, we provide here for the first time 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 antitumor immune responses in breast cancer patients. The HLA Class II tetramers used in this study may constitute a valuable tool to elucidate the role of antigen-specific Tregs in breast cancer immunity and to monitor breast cancer-specific CD4+ T cells.
PMCID: PMC3716760  PMID: 23894725
breast cancer; mammaglobin; HLA Class II; multimer; regulatory T cells; suppression; tetramer; Tregs; tumor-specific T cells
3.  Adjuvant Systemic Therapy of Breast Cancer 
Breast Care  2011;6(3):179-183.
The first procedure in primary breast cancer is usually the surgical excision of the tumor. However, a medical therapy is necessary in almost all patients to treat the systemic component of the disease. Which medical approach is recommended depends on the biology of the tumor itself. Endocrine-responsive tumors must be treated by an endocrine therapy according to their menopausal status. In HER2/neu-overexpressing tumors, the monoclonal antibody trastuzumab is part of the standard treatment in combination with chemotherapy. Hormone receptor-negative and non-HER2/neu-overexpressing tumors as well as endocrine-responsive tumors with a high proliferation index or additional risk factors must be treated with chemotherapy as well. This review article gives further information about the available agents and schedules.
PMCID: PMC3132964  PMID: 21779222
Breast cancer; Adjuvant therapy; Chemotherapy; Endocrine therapy
4.  Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors 
Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA– memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells.
PMCID: PMC437963  PMID: 15232613

Results 1-4 (4)