Effects of distant metastasis and peripheral CA 15-3 on the induction of spontaneous T cell responses in breast cancer patients

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

Christoph Domschke1 , Florian Schuetz1, Nora Sommerfeldt2, Joachim Rom1, Alexander Scharf1, Christof Sohn1, Andreas Schneeweiss1 and Philipp Beckhove2

(1) Department of Gynecology and Obstetrics, University Hospital of Heidelberg, Voßstraße 9, 69115 Heidelberg, Germany
(2) Tumor Immunology Program, Division of Translational Immunology, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany