Titre
Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Mondini, M.
Auteure/Auteur
Nizard, M.
Auteure/Auteur
Tran, T.
Auteure/Auteur
Mauge, L.
Auteure/Auteur
Loi, M.
Auteure/Auteur
Clémenson, C.
Auteure/Auteur
Dugue, D.
Auteure/Auteur
Maroun, P.
Auteure/Auteur
Louvet, E.
Auteure/Auteur
Adam, J.
Auteure/Auteur
Badoual, C.
Auteure/Auteur
Helley, D.
Auteure/Auteur
Dransart, E.
Auteure/Auteur
Johannes, L.
Auteure/Auteur
Vozenin, M.C.
Auteure/Auteur
Perfettini, J.L.
Auteure/Auteur
Tartour, E.
Auteure/Auteur
Deutsch, E.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1538-8514
Statut éditorial
Publié
Date de publication
2015
Volume
14
Numéro
6
Première page
1336
Dernière page/numéro d’article
1345
Peer-reviewed
Oui
Langue
anglais
Résumé
There is growing interest in the association of radiotherapy and immunotherapy for the treatment of solid tumors. Here, we report an extremely effective combination of local irradiation (IR) and Shiga Toxin B (STxB)-based human papillomavirus (HPV) vaccination for the treatment of HPV-associated head and neck squamous cell carcinoma (HNSCC). The efficacy of the irradiation and vaccine association was tested using a model of HNSCC obtained by grafting TC-1/luciferase cells at a submucosal site of the inner lip of immunocompetent mice. Irradiation and the STxB-E7 vaccine acted synergistically with both single and fractionated irradiation schemes, resulting in complete tumor clearance in the majority of the treated mice. A dose threshold of 7.5 Gy was required to elicit the dramatic antitumor response. The combined treatment induced high levels of tumor-infiltrating, antigen-specific CD8(+) T cells, which were required to trigger the antitumor activity. Treatment with STxB-E7 and irradiation induced CD8(+) T-cell memory, which was sufficient to exert complete antitumor responses in both local recurrences and distant metastases. We also report for the first time that a combination therapy based on local irradiation and vaccination induces an increased pericyte coverage (as shown by αSMA and NG2 staining) and ICAM-1 expression on vessels. This was associated with enhanced intratumor vascular permeability that correlated with the antitumor response, suggesting that the combination therapy could also act through an increased accessibility for immune cells. The combination strategy proposed here offers a promising approach that could potentially be transferred into early-phase clinical trials.
Sujets
PID Serval
serval:BIB_12931D59EDB4
PMID
Open Access
Oui
Date de création
2015-08-24T15:51:30.819Z
Date de création dans IRIS
2025-05-20T16:47:27Z