Profiling HPV-16–specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients
| Autor: | Corey Smith, Sriganesh Srihari, Kunal H. Bhatt, Howard Liu, Sandro V. Porceddu, Liz Kenny, Michelle A Neller, Lea Lekieffre, Pauline Crooks, Rajiv Khanna, Blake T. Aftab |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Tumor Immunology Oncology medicine.medical_specialty Multivariate analysis T-Lymphocytes T cell Immunology CD8-Positive T-Lymphocytes T cell response Article Antigen Antigens Neoplasm Internal medicine medicine T cell immunity Humans Immunology and Allergy Human papillomavirus 16 business.industry Papillomavirus Infections Case-control study virus diseases Middle Aged Oropharyngeal Neoplasms stomatognathic diseases medicine.anatomical_structure Case-Control Studies Cohort Female business CD8 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20200389 |
| Popis: | Proteome-wide profiling of HPV-specific T cell immunity in oropharyngeal cancer (OPC) patients reveals broad and multiple antigen-specific reactivities directed to HPV-encoded proteins E1, E2, E4, E5 E6, E7, and L1. These observations provide novel insights for future development of cellular immunotherapies for HPV-associated OPC patients. 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. Graphical Abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|