The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients.
We analyzed the T-cell repertoires from the bone marrow of 39 primary operated breast cancer patients and 11 healthy female donors for the presence and frequencies of spontaneously induced effector/memory T lymphocytes with peptide-HLA-A2-restricted reactivity against 10 breast tumor-associated antigens (TAA) and 3 normal breast tissue-associated antigens by short-term IFN-gamma enzyme-linked immunospot (ELISpot) analysis. Sixty-seven percent of the patients recognized TAAs with a mean frequency of 144 TAA reactive cells per 10(6) T cells. These patients recognized simultaneously an average of 47% of the tested TAAs. The T-cell repertoire was highly polyvalent and exhibited pronounced interindividual differences in the pattern of TAAs recognized by each patient. Strong differences of reactivity were noticed between TAAs, ranging from 100% recognition of prostate-specific antigen(p141-149) to only 25% recognition of MUC1(p12-20) or Her-2/neu(p369-377). In comparison with TAAs, reactivity to normal breast tissue-associated antigens was lower with respect to the proportions of responding patients (30%) and recognized antigens (27%), with a mean frequency of only 85/10(6) T cells. Healthy individuals also contained TAA-reactive T cells but this repertoire was more restricted and the frequencies were in the same range as T cells reacting to normal breast tissue-associated antigens. Our data show a highly individual T-cell repertoire for recognition of TAAs in breast cancer patients. This has potential relevance for T-cell immune diagnostics, for tumor vaccine design, and for predicting immune responsiveness.
Sommerfeldt
Nora
N
Department of Cellular Immunology, The German Cancer Research Center, Heidelberg, Germany.
Schütz
Florian
F
Sohn
Christoph
C
Förster
Joanna
J
Schirrmacher
Volker
V
Beckhove
Philipp
P
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015234:HLA-A Antigens / Q000032:analysis / Q000737:chemistry; D015789:HLA-A2 Antigen; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments