Fiche publication
Date publication
janvier 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CLAVEL Christine
,
Dr DALSTEIN Véronique
,
Dr GUIHARD Sébastien
,
Dr JUNG Alain
,
Mme LEDRAPPIER Sonia
,
Pr NOEL Georges
,
Dr WASYLYK Bohdan
Tous les auteurs :
Jung AC, Guihard S, Krugell S, Ledrappier S, Brochot A, Dalstein V, Job S, de Reynies A, Noel G, Wasylyk B, Clavel C, Abecassis J
Lien Pubmed
Résumé
Patients with human papillomavirus (HPV)-related oropharyngeal tumors display improved prognosis. The biological basis of this tumor phenotype is poorly understood. We investigated whether increased lymphocyte infiltrate in HPV-positive oropharyngeal squamous cell carcinomas could account for better prognosis. We previously identified, in an Affymetrix GeneChip analysis of 83 HPV-unrelated and 11 HPV-related squamous cell carcinoma of the oropharynx, several candidate genes, including CD8alpha and CD3zeta. Their expression was validated in this study by qRT-PCR on an independent clinical series of 144 oropharyngeal tumors. Immunohistochemical staining of tumor specimens was performed to evaluate infiltration of tumor stroma by CD8+ and CD4+ lymphocytes. The prognostic value of CD8alpha and CD3zeta expression levels was measured by Kaplan-Meier and Cox regression model analyses. Immune response-related signaling pathways were found to be deregulated in HPV-positive oropharyngeal tumors. Expression of CD8alpha, CD3zeta, granzyme K, CD28 and integrin alphaL RNAs was upregulated in HPV-positive lesions when compared with HPV-unrelated tumors (p < 0.05). Stroma of HPV-positive tumors was frequently and strongly infiltrated by CD8alpha- and CD3zeta-positive T cells. CD8alpha RNA expression correlated with both improved global (Kaplan-Meier; p = 0.005; Cox regression: p = 0.003) and disease-free (Cox regression: p = 0.04) survival. CD3zeta RNA expression correlated with improved overall survival (Cox regression: p = 0.024). These results suggest that an increased cytotoxic T-cell-based antitumor immune response is involved in improved prognosis of patients with HPV-positive tumors.
Référence
Int J Cancer. 2013 Jan 15;132(2):E26-36
