Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cancer Immunology, Immunotherapy Année : 2008

Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses.

Résumé

PURPOSE: Electrochemotherapy (ECT) is an effective local therapy of human cutaneous cancers but has no effect on distant untreated tumors. We addressed whether tumor-associated antigens released after ECT could induce an efficient systemic immunity when associated with an appropriate immunoadjuvant. METHODS AND RESULTS: We first studied the nature of the cellular recruitment and the expression of various toll-like receptors (TLRs) in tumors treated by ECT. We found that ECT induced a massive recruitment of CD11c and CD11b positive cells in the tumors and a strong increase of TLR9 expression. We then tested antitumor effects of the combination: ECT followed by TLR-9 ligands, CpG oligodeoxynucleotides (CpG ODN), in three murine tumor models. We found that this combination triggered both potent local synergistic antitumor effects, on the ipsi-lateral ECT-treated tumor, and more interestingly, a systemic antitumor response on the contra-lateral untreated tumor, in the three models. The systemic protection was T-cell dependent as it was not observed in nude littermates. The combination induced tumor-specific T cell effectors in the tumor-draining lymph nodes and in the spleen which secreted significantly more gamma-interferon upon activation than with ECT or CpG ODN alone. CONCLUSIONS: Our data show that ECT and CpG ODN synergize and induce a significant increase of the local effect and a systemic T-dependent antitumor response. Such combination constitutes a potential innovative vaccination strategy using in situ tumor-associated antigens that could eventually be translated into the clinic.

Dates et versions

hal-00319924 , version 1 (09-09-2008)

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Stephan Roux, Claire Bernat, Bassim Al-Sakere, François Ghiringhelli, Paule Opolon, et al.. Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses.. Cancer Immunology, Immunotherapy, 2008, 57 (9), pp.1291-300. ⟨10.1007/s00262-008-0462-0⟩. ⟨hal-00319924⟩
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