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CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer

Masterson, L, Lechner, M, Loewenbein, S, Mohammed, H, Davies-Husband, C, Fenton, TR, Sudhoff, H, Jani, P, Goon, P, Sterling, J and others. (2016) CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer. European Journal of Cancer, 67 (C). pp. 141-151. ISSN 0959-8049. (doi:10.1016/j.ejca.2016.08.012) (KAR id:61501)

Abstract

Introduction: Immunological response to human papillomavirus (HPV) in the development and progression of HPV16+ oropharyngeal squamous cell carcinoma (OPSCC) (accounting for the majority of viral associated cases) is largely unknown and may provide important insights for new therapeutic strategies.

Methods: In this prospective clinical trial (UKCRN11945), we examined cell-mediated immune responses to HPV16 E2, E6 and E7 in peripheral blood using IFN-γ enzyme-linked immunosorbent spot assay. CD56+, CD4+, CD8+ and regulatory T cell frequencies were also discerned by flow cytometry. Fifty-one study participants with oropharyngeal carcinoma were recruited. Control subjects were those undergoing tonsillectomy for benign disease. All patients were treated with curative intent by radiotherapy ± chemotherapy. Disease-specific survival was investigated by multivariate analysis.

Results: HPV16 DNA was detected in 41/51 of the OPSCC participants. T cell responses against HPV16 E6 or E7 peptides were detected in 33/51 evaluable patients, respectively and correlated with HPV status. Matched pre- and post-treatment T cell responses were available for 39/51 OPSCC cases. Within the whole cohort, elevated post-treatment CD8+ response to HPV16 E7 correlated with longer disease free survival (multivariate DFS p < 0.03). Within the HPV + OPSCC cohort, a significant increase in regulatory T cells (p < 0.02) was noted after treatment.

Conclusions: This is the first study to provide survival data in OPSCC stratified by cell-mediated immune response to HPV16 peptides. Within the HPV16+ OPSCC cohort, enhanced immunoreactivity to antigen E7 was linked to improved survival. An increase in regulatory T cell frequencies after treatment may suggest that immunosuppression can contribute to a reduced HPV-specific cell-mediated response.

Item Type: Article
DOI/Identification number: 10.1016/j.ejca.2016.08.012
Additional information: publisher: Elsevier articletitle: CD8+ T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer journaltitle: European Journal of Cancer articlelink: http://dx.doi.org/10.1016/j.ejca.2016.08.012 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.
Uncontrolled keywords: Human papillomavirus; Oropharyngeal carcinoma; Cell-mediated immunity; Interferon-?, School of Biosciences
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Tim Fenton
Date Deposited: 21 Apr 2017 13:28 UTC
Last Modified: 08 Jan 2022 23:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61501 (The current URI for this page, for reference purposes)

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