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Expression of TLR9 within human glioblastoma

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Abstract

Immunostimulating oligonucleotides containing CpG motifs (CpG-ODN) have shown promising antitumor activity in preclinical glioma models. CpG motifs are specifically recognized by the Toll-like receptor 9 (TLR9), mainly expressed in plasmacytoid dendritic cells (pDCs) and B cells. Expression of TLR9 within human glioma samples has not been investigated. As CpG-ODN is currently under clinical trials in glioma patients, we investigated whether TLR9 is expressed at the RNA levels in a series of 37 human glioblastomas (GBM) by quantitative PCR. TLR9 expression was detected at variable levels, which might suggest that some patients are more likely to benefit from treatment with CpG-ODN than others. No significant relationships between TLR9 expression and age, sex, tumor location, lymphocytes infiltration, oligodendroglial components or survival were found. TLR9 is unlikely to be expressed by tumor cells as no TLR9 expression was detected in pure human GBM xenografts. Immunocytochemistry studies showed TLR9 expression in some macrophages/microglial cells. The expression of TLR9 within human GBM strengthens the rationale for the utilization of CpG-ODN in this disease.

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Abbreviations

TLR:

Toll like receptor

GBM:

Glioblastoma

ODN:

Oligodeoxynucleotides

CpG-ODN:

ODN containing a cytosine-guanosine motif

NK:

Natural killer

DC:

Dendritic cell

pDC:

Plasmacytoid DC

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Acknowledgments

This work was supported by the Association Oligocyte, the Association pour la Recherche sur les Tumeurs cérébrales (ARTC), the Institut National de la Santé et de la Recherche Médicale (INSERM), the University Pierre & Marie Curie (Paris VI), and the Assistance Publique des Hôpitaux de Paris (AP/HP). Potential conflict of interest: The Assistance Publique-Hopitaux de Paris and Antoine Carpentier hold a patent position on immunotherapy with CpG-ODN.

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Authors and Affiliations

  1. INSERM, U711, Biologie des Interactions Neurones & Glie, Paris, France

    Yuxia Meng, Michèle Kujas, Yannick Marie, Sophie Paris, Joëlle Thillet, Jean-Yves Delattre & Antoine F. Carpentier

  2. Service de Neurologie Mazarin de l’Hôpital Pitié-Salpêtrière, Paris, 75013, France

    Jean-Yves Delattre

  3. Service de Neurologie de l’Hôpital Avicenne, 125 route de Stalingrad, Bobigny, 93009, France

    Antoine F. Carpentier

  4. Assistance Publique des Hôpitaux de Paris, Paris, France

    Michèle Kujas, Jean-Yves Delattre & Antoine F. Carpentier

  5. UFR de Santé, Médecine et Biologie Humaine de Bobigny – Université Paris 13, Paris, France

    Antoine F. Carpentier

Authors
  1. Yuxia Meng
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  2. Michèle Kujas
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  3. Yannick Marie
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  4. Sophie Paris
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  5. Joëlle Thillet
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  6. Jean-Yves Delattre
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  7. Antoine F. Carpentier
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Corresponding author

Correspondence to Antoine F. Carpentier.

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Meng, Y., Kujas, M., Marie, Y. et al. Expression of TLR9 within human glioblastoma. J Neurooncol 88, 19–25 (2008). https://doi.org/10.1007/s11060-008-9536-2

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  • DOI: https://doi.org/10.1007/s11060-008-9536-2

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