Effects of distant metastasis and peripheral CA 15-3 on the induction of spontaneous T cell responses in breast cancer patients |
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Authors: | Christoph Domschke Florian Schuetz Nora Sommerfeldt Joachim Rom Alexander Scharf Christof Sohn Andreas Schneeweiss Philipp Beckhove |
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Institution: | 1. Department of Gynecology and Obstetrics, University Hospital of Heidelberg, Vo?stra?e 9, 69115, Heidelberg, Germany 2. Tumor Immunology Program, Division of Translational Immunology, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany
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Abstract: | Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they
can be reactivated to IFN-γ producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID
mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific
tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-γ
EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory
T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A*0201-restricted peptides from the tumor-associated antigens MUC1, Hpa16–24 and Hpa183–191 was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific
cellular immune responses in the human BM. |
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