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Upregulation of antigen-processing machinery components at mRNA level in acute lymphoblastic leukemia cells after CD40 stimulation

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Abstract

The development of immunotherapy in hematologic malignancies has been observed in the last few years. One of the approaches is the use of cancer vaccines based on leukemia-derived dendritic cells (DC). Recent studies from our laboratory and other laboratories have shown that CD40 stimulation improves leukemia cells immunogenicity and generates an antitumor immune response. The design of future cancer vaccines requires the knowledge concerning the function of dendritic cells including antigen processing. The aim of our present study was the assessment of antigen-processing machinery (APM) components in acute lymphoblastic leukemia (ALL) cells before and after CD40 stimulation at messenger RNA (mRNA) level. Twenty-five children with ALL were enrolled into the study. Leukemic cells were stimulated (or not) with CD40L and IL-4. Elements of the antigen-processing machinery (MB1, LMP2, LMP7, LMP10, TAP1, TAP2, calnexin, calreticulin, tapasin, ERp57, zeta, delta) were determined by real-time PCR technique. The expression of important costimulatory and adhesion molecules considered as DC markers (CD40, CD54, CD80, CD83, CD86) were determined at the mRNA (PCR) and protein (flow cytometry) levels. The following are the results of our study: (1) We noted an upregulation of all costimulatory and adhesion molecules at the mRNA and protein levels in ALL cells after the culture; (2) the significant rise in expression of nearly all APM components after CD40 stimulation was observed. This confirms specific stimulation of the antigen-processing system in ALL cells by CD40L. Future work should focus on the clinical significance of these findings for immunotherapy in leukemias.

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Abbreviations

ALL:

acute lymphoblastic leukemia

APM:

antigen processing machinery

beta2M:

beta2-microglobulin

CAL:

calnexin

DC:

dendritic cells

EBV:

Ebstein–Barr virus

ER:

endoplasmic reticulum

LMP:

low-molecular-mass polypeptide

TAP:

transporter associated with antigen presentation

TNFR:

tumor necrosis factor receptor

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Authors and Affiliations

  1. Department of Pediatric Oncology, Medical University of Białystok, 15-274, Bialystok, Poland

    Włodzimierz Łuczyński & Maryna Krawczuk-Rybak

  2. Department of Clinical Molecular Biology, Medical University of Białystok, Białystok, Poland

    Oksana Kowalczuk

  3. Department of Cytogenetics, Medical University of Białystok, Białystok, Poland

    Elżbieta Iłendo

  4. Flow Cytometry Unit, Medical University of Białystok, Białystok, Poland

    Anna Stasiak-Barmuta

Authors
  1. Włodzimierz Łuczyński
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  2. Oksana Kowalczuk
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  3. Elżbieta Iłendo
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  4. Anna Stasiak-Barmuta
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  5. Maryna Krawczuk-Rybak
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Correspondence to Włodzimierz Łuczyński.

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Łuczyński, W., Kowalczuk, O., Iłendo, E. et al. Upregulation of antigen-processing machinery components at mRNA level in acute lymphoblastic leukemia cells after CD40 stimulation. Ann Hematol 86, 339–345 (2007). https://doi.org/10.1007/s00277-007-0256-z

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  • DOI: https://doi.org/10.1007/s00277-007-0256-z

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