Coexpression of CD40L and CD70 by semiallogenic tumor cells induces anti-tumor immunity
| Autor: | Anne-Françoise Tilkin-Mariamé, Carine Cormary, Gilles Favre, Bernard Mariamé, Elsa Hiver |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
T-Lymphocytes CD40 Ligand chemical and pharmacologic phenomena Lymphocyte Activation Mice Immune system Antigen Antigens CD Cell Line Tumor Neoplasms MHC class I medicine Animals Cytotoxic T cell Molecular Biology Cell Proliferation CD40 biology Melanoma Cell Membrane Histocompatibility Antigens Class I Membrane Proteins medicine.disease Gene Expression Regulation Neoplastic Killer Cells Natural Tumor Escape Tumor Necrosis Factors Immunology biology.protein Cancer research Molecular Medicine Female Immunotherapy Neoplasm Transplantation CD8 CD27 Ligand |
| Zdroj: | Cancer Gene Therapy. 12:963-972 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700861 |
| Popis: | 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-2K(d)) molecule expression on melanoma cells (B16F10, H-2(b)) 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-2K(d)) enhances this effect. Growth kinetics of mock and CD40L-CD70-H-2K(d)-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-2K(d)-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-2K(d) B16F10 tumor cells improved the generation of cytotoxic lymphocytes against the wild-type melanoma cells expressing the syngenic MHC Class I molecule H-2K(b) (B16K1). These observations lay a path for new immunotherapeutic trials using semiallogenic fibroblasts expressing costimulatory molecules and tumor-associated antigens. |
| Databáze: | OpenAIRE |
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