Cyclin D1 as a universally expressed mantle cell lymphoma-associated tumor antigen for immunotherapy.
Mantle cell lymphoma (MCL) accounts for 5-10% of all non-Hodgkin lymphomas and has the worst prognosis among all lymphomas. The hallmark of MCL is a t(11;14) translocation that results in overexpression of cyclin D1 by tumor cells of virtually all patients. In this study, we examined whether cyclin D1 could be an effective tumor-associated antigen for immunotherapy. We identified cyclin D1 peptides for HLA-A(*)0201 and generated peptide-specific CD8(+) T-cell lines from HLA-A(*)0201(+) blood donors and MCL patients. These cell lines proliferated in response to cyclin D1 peptide-pulsed stimulatory cells. Moreover, the T cells efficiently lysed peptide-pulsed but not unpulsed T2 cells and autologous dendritic cells; cyclin D1(+) and HLA-A(*)0201(+) human MCL lines MINO, SP53, Jeko-1 and Granta 519; and more importantly, HLA-A(*)0201(+) primary lymphoma cells from MCL patients. No killing was observed with HLA-A(*)0201(-) primary lymphoma cells or HLA-A(*)0201(+) normal blood cells, including B cells. These results indicate that these T cells are potent cytotoxic T cells and recognize cyclin D1 peptides naturally presented by patient lymphoma cells in the context of HLA-A(*)0201 molecules. Taken together, our work identifies cyclin D1 as a potentially important antigen for immunotherapy of MCL.
Wang
M
M
Division of Cancer Medicine, Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Sun
L
L
Qian
J
J
Han
X
X
Zhang
L
L
Lin
P
P
Cai
Z
Z
Yi
Q
Q
D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000737:chemistry / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D020522:Lymphoma, Mantle-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000276:immunology
D019938:Cyclin D1; D007371:Interferon-gamma