Cyclin D1 as a universally expressed mantle cell lymphoma-associated tumor antigen for immunotherapy

M. Wang, L. Sun, J. Qian, X. Han, L. Zhang, P. Lin, Z. Cai, Q. Yi

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1320-1328
Number of pages9
JournalLeukemia
Volume23
Issue number7
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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