Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-α hybrid protein by lymphocytes of acute promyelocytic leukemia patients

Said Dermime, Carla Bertazzoli, Edoardo Marchesi, Fernando Ravagnani, Kurt Blaser, Gian Marco Corneo, Enrico Pogliani, Giorgio Parmiani, Carlo Gambacorti-Passerini

Research output: Contribution to journalArticlepeer-review

Abstract

In previous studies, it was shown that the fusion region of the pml/RAR-α protein, expressed by acute promyelocytic leukemia (APL) cells, can be specifically recognized in vitro by donor (D. E.) CD4 T cells in a HLA class II DR11-restricted fashion. We present here the results on the recognition of several pml/RAR-α peptides by APL patients expressing HLA DR11. The in vitro immunization of peripheral blood lymphocytes from four patients in remission (S. R., F. R., M. M., P.G.) with BCR1/25, a 25-mer pml/ RAR-α, did not elicit either a polyclonal or a clonal immune response specific to tile peptide. We then generated new donor anti-pml/RAR-α CD4+ T cell clones. These clones were tested for their recognition of BCR1/25. One clone (C3/5, CD3+, CD4+, CD8-) was selected for further analysis. Clone C3/5 showed specific proliferation, cytotoxicity, and cytokine (tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25, C3/5 cells developed specific proliferation and cytotoxicity when challenged with peptide-pulsed lymphoblastic cell lines and peripheral blood lymphocytes from the four DR11+ APL patients. APL blasts, available only from patients F. R, and. P. G., were not lysed by C3/5 and were unable to present peptide BCR1/25. Incubation of APL cells with IFN-γ failed to induce HLA class II molecules and recognition by the C3/5 clone. Since APL cells do not express HLA class II molecules, we tested in two donors (D. E. and C. H. R.) and in patients S. R. and P. G. whether the use of 9-mer peptides (BCR1/9) would generate a CD8/HLA class I-restricted response. No peptide-specific T-cell line or clone could be generated from both donors and patients. These findings are discussed in relation to possible therapeutic approaches to the immunotherapy of APL.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalClinical Cancer Research
Volume2
Issue number3
Publication statusPublished - Mar 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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