Liam Masterson1, Matt Lechner2, Sarah Loewenbein3, Hassan Mohammed4, Cameron Davies-Husband5, Tim Fenton2, Holger Sudhoff6, Piyush Jani5, Peter Goon7, Jane Sterling7. 1. Department of Pathology, University of Cambridge, UK; Department of Otorhinolaryngology, Cambridge University Hospitals NHS Foundation Trust (CUHT), UK. Electronic address: lmm398@doctors.org.uk. 2. UCL Cancer Institute, London, UK. 3. Department of Pathology, University of Cambridge, UK. 4. Barts Health NHS Trust, London, UK. 5. Department of Otorhinolaryngology, Cambridge University Hospitals NHS Foundation Trust (CUHT), UK. 6. Department of Otolaryngology, Head and Neck Surgery, Bielefeld Academic Teaching Hospital, Germany. 7. Department of Pathology, University of Cambridge, UK; Department of Dermatology, CUHT, UK.
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.
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.
Authors: Yasmin Hasan; Larissa Furtado; Ana Tergas; Nita Lee; Rebecca Brooks; Anne McCall; Daniel Golden; Shruti Jolly; Gini Fleming; Matthew Morrow; Kimberly Kraynyak; Albert Sylvester; Fauzia Arif; Matt Levin; David Schwartz; Jean Boyer; Jeffrey Skolnik; Mark Esser; Rakesh Kumar; Mark Bagarazzi; Ralph Weichselbaum; Michael Spiotto Journal: Int J Radiat Oncol Biol Phys Date: 2020-03-07 Impact factor: 7.038
Authors: Xuqing Zhang; Mengyao Luo; Shamael R Dastagir; Mellissa Nixon; Annie Khamhoung; Andrea Schmidt; Albert Lee; Naren Subbiah; Douglas C McLaughlin; Christopher L Moore; Mary Gribble; Nicholas Bayhi; Viral Amin; Ryan Pepi; Sneha Pawar; Timothy J Lyford; Vikram Soman; Jennifer Mellen; Christopher L Carpenter; Laurence A Turka; Thomas J Wickham; Tiffany F Chen Journal: Nat Commun Date: 2021-05-11 Impact factor: 14.919