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Letter to the Editor

Imatinib does not impair specific antitumor T-cell immunity in patients with chronic myeloid leukemia

Leukemia volume 20, pages 142–143 (2006)Cite this article

Imatinib mesylate is currently the most effective treatment that induces complete remission of chronic myeloid leukemia (CML). However, residual disease may re-expand in some cases and a vaccine-based immunological attack can further reduce the tumor burden.1, 2 In this setting, effects of imatinib on immune function may be of concern.3 Studies in vitro have indicated that imatinib inhibits TCR-mediated T-cell activation and proliferation against viral or other immunogenic antigens.4, 5 One study in mice suggested that imatinib impaired in vitro T-cell proliferation and in vivo delayed-type hypersensitivity (DTH).6 T-cell inhibition may associate with defective antigen presentation by dendritic cells.7 Others, however, propose that in vitro exposure to imatinib enhances antigen presentation.8

In a recent study, we evaluated the ability of 10 CML patients, with persistent minimal residual disease during prolonged treatment with imatinib, to raise specific antitumor T-cell responses after immunization with weakly immunogenic p210-derived peptide antigens associated to QS-21 and GM-CSF as immunological adjuvants.2 Peptide-specific immune responses were measured at baseline and after six vaccinations in all patients by DTH in vivo test and a proliferation assay with unprimed CD4+ cells.2 As an expansion of this previous study, we report additional immunological data on a total of 16 CML imatinib-treated patients and compare their immune responses with a cohort of seven immunized patients in minimal residual disease during INF-α (Table 1).

Table 1 Evaluation of peptide specific DTH response in vivo and peptide specific CD4+ cell proliferation in vitro after six vaccinations with CML-derived peptides in CML patients during imatinib or IFN-α treatment
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References

  1. Kurbegov D, Molldrem JJ . Immunity to chronic myelogenous leukemia. Hematol Oncol Clin North Am 2004; 18: 733–752.

    Article  Google Scholar 

  2. Bocchia M, Gentili S, Abruzzese E, Fanelli A, Iuliano F, Tabilio A et al. Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet 2005; 365: 657–662.

    Article  CAS  Google Scholar 

  3. Maziarz RT . Imatinib mesylate: a novel immune suppressive agent? Blood 2004; 104: 914–915.

    Article  CAS  Google Scholar 

  4. Seggewiss R, Lore K, Greiner E, Magnusson MK, Price DA, Douek DC et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood 2005; 105: 2473–2479.

    Article  CAS  Google Scholar 

  5. Cwynarski K, Laylor R, Macchiarulo E, Goldman J, Lombardi G, Melo JV et al. Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro. Leukemia 2004; 18: 1332–1339.

    Article  CAS  Google Scholar 

  6. Dietz AB, Souan L, Knutson GJ, Bulur PA, Litzow MR, Vuk-Pavlovic S . Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood 2004; 104: 1094–1099.

    Article  CAS  Google Scholar 

  7. Appel S, Boehmler AM, Grunebach F, Muller MR, Rupf A, Weck MM et al. Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells. Blood 2004; 103: 538–544.

    Article  CAS  Google Scholar 

  8. Wang H, Cheng F, Cuenca A, Horna P, Zheng Z, Bhalla K et al. Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance. Blood 2005; 105: 1135–1143.

    Article  CAS  Google Scholar 

  9. Steegmann JL, Moreno G, Alaez C, Osorio S, Granda A, de la Camara R et al. Chronic myeloid leukemia patients resistant to or intolerant of interferon alpha and subsequently treated with imatinib show reduced immunoglobulin levels and hypogammaglobulinemia. Haematologica 2003; 88: 762–768.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by grants from PAR 2003, MIUR 2003, SIENAIL, Fondazione Monte dei Paschi, EHA clinical research grant 2004. The study was performed after approval by the local ethical committee and informed consent was obtained before patients were entered into the study.

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Authors and Affiliations

  1. Department of Hematology, University of Siena, Siena, Italy

    M Bocchia, F Forconi, M Ippoliti, M T Pirrotta, D Raspadori, M Tozzi, A Gozzetti & F Lauria

  2. Department of Hematology, Roma ‘Tor Vergata’ University, Roma, Italy

    E Abruzzese & M M Trawinska

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  1. M Bocchia
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Bocchia, M., Abruzzese, E., Forconi, F. et al. Imatinib does not impair specific antitumor T-cell immunity in patients with chronic myeloid leukemia. Leukemia 20, 142–143 (2006). https://doi.org/10.1038/sj.leu.2404029

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