CD8-alpha T-cell infiltration in human papillomavirus-related oropharyngeal carcinoma correlates with improved patient prognosis

Authors

  • Alain C. Jung,

    Corresponding author
    1. Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
    • Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, 67065 Strasbourg, Cedex, France
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    • Tel.: +33-388-25-24-43, Fax: +33-388-25-85-00

  • Sébastien Guihard,

    1. Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
    2. Département de Radiothérapie, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
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  • Sylvie Krugell,

    1. Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
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  • Sonia Ledrappier,

    1. Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
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  • Alexandra Brochot,

    1. INSERM UMRS 903, Laboratoire Pol Bouin, CHU Reims, 45 Rue Cognacq-Jay, Reims, France
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  • Véronique Dalstein,

    1. INSERM UMRS 903, Laboratoire Pol Bouin, CHU Reims, 45 Rue Cognacq-Jay, Reims, France
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  • Sylvie Job,

    1. Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Paris, 14 Rue Corvisart, Paris, France
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  • Aurélien de Reynies,

    1. Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Paris, 14 Rue Corvisart, Paris, France
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  • Georges Noël,

    1. Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
    2. Département de Radiothérapie, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
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  • Bohdan Wasylyk,

    1. IGBMC, UMR7104 CNRS/UDS, U964 INSERM, 1 Rue Laurent Fries, Illkirch Graffenstaden, France
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  • Christine Clavel,

    1. INSERM UMRS 903, Laboratoire Pol Bouin, CHU Reims, 45 Rue Cognacq-Jay, Reims, France
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  • Joseph Abecassis

    1. Laboratoire de Biologie Tumorale, EA3430, Centre Régional de Lutte Contre le Cancer Paul Strauss, 3 Rue de la Porte de l'Hôpital, Strasbourg, France
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Abstract

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 CD8α and CD3ζ. 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 CD8α and CD3ζ 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 CD8α, CD3ζ, granzyme K, CD28 and integrin αL 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 CD8α- and CD3ζ-positive T cells. CD8α 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. CD3ζ 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.

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