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

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-gamma 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-gamma 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, Hpa(16-24) and Hpa(183-191) 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.