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Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

Leukemia volume 18, pages 1223–1230 (2004)Cite this article

Abstract

Chemotherapeutic drugs kill cancer cells mainly by direct cytotoxicity, but they might also induce a stronger host immune response by causing the tumor to produce costimulatory cell surface molecules like CD80. We previously reported that in myeloid leukemic cells, γ-irradiation induced CD80 expression. In this study, we show that cytosine arabinoside (Ara-C), even at low doses, induced CD80 expression in vitro in mouse DA1-3b leukemic cells, by a mechanism that involved reactive oxygen species. In vivo experiments in the mouse DA1-3b/C3H whole-animal acute myeloid leukemia (AML) model showed that injection of Ara-C induced expression of CD80 and CD86, and decreased expression of B7-H1, indicating that chemotherapy can modify costimulatory molecule expression in vivo, in a way not necessarily observed in vitro. Mouse leukemic cells exposed in vivo to Ara-C were more susceptible to specific cytotoxic lymphocyte (CTL)-mediated killing. Ara-C also induced CD80 or CD86 expression in 14 of 21 primary cultured human AML samples. In humans being treated for AML, induction chemotherapy increased CD86 expression in the leukemic cells. These findings indicate possible synergistic strategies between CTL-based immunotherapy and chemotherapy for treatment. They also suggest an additional mechanism by which chemotherapy can eradicate AML blasts.

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Acknowledgements

This work was supported by the Ligue Contre le Cancer (Comité du Nord and Comité du Pas de Calais), the Association de Recherche sur le Cancer, the Fondation contre la Leucémie, and The Centre Hospitalier Universitaire of Lille, France. RV is a recipient of a grant from the Institut de Recherche sur le Cancer de Lille, while AS is a recipient of a grant from the Region Nord-Pas-de-Calais/CHRU de Lille.

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Author notes

  1. R Vereecque and A Saudemont: The two first authors contributed equally to this work

Authors and Affiliations

  1. Unité INSERM 524, Institut de Recherche sur le Cancer de Lille, Lille, France

    R Vereecque, A Saudemont & B Quesnel

  2. Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France

    R Vereecque, A Saudemont & B Quesnel

  3. Service des Maladies du Sang, Centre Hospitalier et Universitaire de Lille, Lille, France

    B Quesnel

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  1. R Vereecque
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  2. A Saudemont
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  3. B Quesnel
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Correspondence to B Quesnel.

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Vereecque, R., Saudemont, A. & Quesnel, B. Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells. Leukemia 18, 1223–1230 (2004). https://doi.org/10.1038/sj.leu.2403391

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