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Coexpression of CD40L and CD70 by semiallogenic tumor cells induces anti-tumor immunity

Cancer Gene Therapy volume 12, pages 963–972 (2005)Cite this article

Abstract

The immune system is potentially qualified to detect and eliminate tumor cells, but various mechanisms developed by tumor cells allow tumor escape. Strategies selected to promote antitumor responses have included genetic modifications of tumor cells to induce expression of costimulatory molecules. Moreover, alloantigens can also act as strong enhancers of the immune response. In this work, we have associated the expression of two costimulatory members of the TNF superfamily, CD40L and CD70 along with an allogenic MHC Class I (H-2Kd) molecule expression on melanoma cells (B16F10, H-2b) to favor the antitumor immune response. B16F10 tumor growth slows significantly when CD40L and CD70 are coexpressed by tumor cells and the association with the allogenic molecule (H-2Kd) enhances this effect. Growth kinetics of mock and CD40L-CD70-H-2Kd-expressing B16F10 tumors in immunocompetent versus nu/nu and beige mice suggested that CD8+ T lymphocytes and NK cells were involved in this antitumor immunity. A delay in mock tumor growth was observed when CD40L-CD70-H-2Kd-expressing B16F10 cells and mock tumor cells were injected simultaneously and contralaterally. It was also shown that in vivo immunization of immunocompetent mice with CD40L-CD70-H-2Kd B16F10 tumor cells improved the generation of cytotoxic lymphocytes against the wild-type melanoma cells expressing the syngenic MHC Class I molecule H-2Kb (B16K1). These observations lay a path for new immunotherapeutic trials using semiallogenic fibroblasts expressing costimulatory molecules and tumor-associated antigens.

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Acknowledgements

This work was supported by the “Institut National de la Santé et de la Recherche Médicale” (INSERM). We thank Dr F Lemonnier from Institut Pasteur (Paris, France), who kindly provided us the vector pKC3-H-2Kd.

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Authors and Affiliations

  1. Département “Innovations thérapeutiques et Oncologie moléculaire”, INSERM U563 CPTP, Institut Claudius Regaud, 20–24 Rue du pont Saint-Pierre, Toulouse Cedex, 31052, France

    Carine Cormary, Elsa Hiver, Gilles Favre & Anne-Françoise Tilkin-Mariamé

  2. Département “Interactions CMV-hôte et réponse immunitaire T antivirale”, INSERM U563 CPTP, CHU Purpan, Toulouse, Cedex 3, 31059, France

    Bernard Mariamé

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  1. Carine Cormary
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  2. Elsa Hiver
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  3. Bernard Mariamé
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  4. Gilles Favre
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  5. Anne-Françoise Tilkin-Mariamé
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Correspondence to Anne-Françoise Tilkin-Mariamé.

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Cormary, C., Hiver, E., Mariamé, B. et al. Coexpression of CD40L and CD70 by semiallogenic tumor cells induces anti-tumor immunity. Cancer Gene Ther 12, 963–972 (2005). https://doi.org/10.1038/sj.cgt.7700861

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