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.
Domschke
Christoph
C
Department of Gynecology and Obstetrics, University Hospital of Heidelberg, Germany. christoph.domschke@med.uni-heidelberg.de
Schuetz
Florian
F
Sommerfeldt
Nora
N
Rom
Joachim
J
Scharf
Alexander
A
Sohn
Christof
C
Schneeweiss
Andreas
A
Beckhove
Philipp
P
D017951:Antigen Presentation / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma; D008213:Lymphocyte Activation; D018396:Mucin-1 / Q000276:immunology*; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology*
D018396:Mucin-1; D007371:Interferon-gamma