Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma.
Multiple myeloma (MM) is one of the most common hematologic malignancies. Despite extensive therapeutical approaches, cures remain rare exceptions. An important issue for future immunologic treatments is the characterization of appropriate tumor-associated antigens. Recently, a highly glycosylated mucin MUC1 was detected on a majority of multiple myeloma cell lines. We analyzed bone marrow and peripheral blood of 68 patients with HLA-A2-positive myeloma for the presence and functional activity of CD8 T cells specific for the MUC1-derived peptide LLLLTVLTV. Forty-four percent of the patients with MM contained elevated frequencies of MUC1-specific CD8 T cells in freshly isolated samples from peripheral blood (PB) or bone marrow (BM) compared with corresponding samples from healthy donors. BM-residing T cells possessed a higher functional capacity upon specific reactivation than PB-derived T cells with regard to interferon gamma (IFN-gamma) secretion, perforin production, and cytotoxicity.
Choi
Carmen
C
Tumor Immunology Program, The German Cancer Research Center, INF 280, 69 120 Heidelberg, Germany.
Witzens
Mathias
M
Bucur
Marianna
M
Feuerer
Markus
M
Sommerfeldt
Nora
N
Trojan
Andreas
A
Ho
Anthony
A
Schirrmacher
Volker
V
Goldschmidt
Hartmut
H
Beckhove
Philipp
P
D000595:Amino Acid Sequence; D000941:Antigens / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001773:Blood Cells / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D006023:Glycoproteins / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D018396:Mucin-1; D009077:Mucins; D009101:Multiple Myeloma / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity
D000941:Antigens; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D015789:HLA-A2 Antigen; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D010446:Peptide Fragments