Enrichment of memory T cells and other profound immunological changes in the bone marrow from untreated breast cancer patients.
Previous studies with animal tumors showed that bone marrow (BM) is a privileged site where potentially lethal tumor cells are controlled in a dormant state by the immune system. Here, we investigated BM of breast cancer patients with respect to tumor cell content, immune activation status and memory T-cell content. BM-derived cells from primary operated breast cancer patients (n = 90) were compared with those from healthy donors (n = 10) and also with cells from respective blood samples. Cytokeratin 19-positive tumor cells were detected by nested polymerase chain reaction. Three-color flow cytometry was used to identify numbers and activation state of T cells, natural killer (NK) cells, monocytes/macrophages and subsets by a panel of monoclonal antibodies (mAbs). The proportion of memory T cells among the CD4 and CD8 T cells was much higher in BM of cancer patients than in healthy donors (p < 0.001). The extent of memory T-cell increase was related to the size of the primary tumor. Patient-derived BM memory CD8 T cells could be shown to contain specific HLA-A2/Her-2/neu(369-377) tetramer binding cells. Patients with disseminated tumor cells in their BM had more memory CD4 T cells and more CD56(+) CD8(+) cells than patients with tumor cell-negative BM. Only some of the immunological changes seen in BM samples of cancer patients were also detectable in peripheral blood samples. Our hypothesis that BM is a special compartment for immunological memory and tumor dormancy is supported by the above findings. The overall results reveal that BM is a valuable additional compartment for immune diagnosis in pathological conditions and possibly for follow-up treatment strategies.
Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
M
M
Feuerer
M
M
Rocha
L
L
Bai
V
V
Umansky
E F
EF
Solomayer
G
G
Bastert
I J
IJ
Diel
V
V
Schirrmacher
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory; D007633:Keratins / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D019002:CD56 Antigen; D015789:HLA-A2 Antigen; D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases