Profiling HPV-16–specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients

KH Bhatt, MA Neller, S Srihari, P Crooks… - Journal of Experimental …, 2020 - rupress.org
KH Bhatt, MA Neller, S Srihari, P Crooks, L Lekieffre, BT Aftab, H Liu, C Smith, L Kenny
Journal of Experimental Medicine, 2020rupress.org
Cellular immunotherapeutics targeting the human papillomavirus (HPV)–16 E6 and E7
proteins have achieved limited success in HPV-positive oropharyngeal cancer (OPC). Here
we have conducted proteome-wide profiling of HPV-16–specific T cell responses in a cohort
of 66 patients with HPV-associated OPC and 22 healthy individuals. Unexpectedly, HPV-
specific T cell responses from OPC patients were not constrained to the E6 and E7 antigens;
they also recognized E1, E2, E4, E5, and L1 proteins as dominant targets for virus-specific …
Cellular immunotherapeutics targeting the human papillomavirus (HPV)–16 E6 and E7 proteins have achieved limited success in HPV-positive oropharyngeal cancer (OPC). Here we have conducted proteome-wide profiling of HPV-16–specific T cell responses in a cohort of 66 patients with HPV-associated OPC and 22 healthy individuals. Unexpectedly, HPV-specific T cell responses from OPC patients were not constrained to the E6 and E7 antigens; they also recognized E1, E2, E4, E5, and L1 proteins as dominant targets for virus-specific CD8+ and CD4+ T cells. Multivariate analysis incorporating tumor staging, treatment status, and smoking history revealed that treatment status had the most significant impact on HPV-specific CD8+ and CD4+ T cell immunity. Specifically, the breadth and overall strength of HPV-specific T cell responses were significantly higher before the commencement of curative therapy than after therapy. These data provide the first glimpse of the overall human T cell response to HPV in a clinical setting and offer groundbreaking insight into future development of cellular immunotherapies for HPV-associated OPC patients.
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