Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment

• Published in: Journal for immunotherapy of cancer Vol. 11; no. 3; p. e006721
• Main Authors: McInnis, Christine, Bhatia, Shilpa, Vijaykumar, Brinda, Tian, Qiaomu, Sun, Yanbo, Leistritz-Edwards, Del, Quinn, Charles T, Uppaluri, Ravi, Egloff, Ann Marie, Srinivasan, Lakshmi, Pregibon, Daniel C, Coyle, Anthony J, Hanna, Glenn J
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-03-2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Adaptive Immunity; Antigens; Basic Tumor Immunology; Breast cancer; Cancer; Cancer therapies; Cells; Gene expression; Head & neck cancer; Head and Neck Neoplasms; Hispanic people; Human papillomavirus; Human papillomavirus 16; Humans; Immunotherapy; Lymphatic system; Lymphocytes; Lymphocytes, Tumor-Infiltrating; Medical prognosis; Metastasis; Oropharyngeal Neoplasms; Papillomavirus Infections; Patients; Peptides; Proteins; Radiation; T-Lymphocytes; Testicular cancer; Throat cancer; Tumor Microenvironment; Tumors; Adaptive Immunity; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; T-Lymphocytes; Head and Neck Neoplasms
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2023-006721

BackgroundHigh-risk human papillomavirus (HPV) is a primary cause of an increasing number of oropharyngeal squamous cell carcinomas (OPSCCs). The viral etiology of these cancers provides the opportunity for antigen-directed therapies that are restricted in scope compared with cancers without viral components. However, specific virally-encoded epitopes and their corresponding immune responses are not fully defined.MethodsTo understand the OPSCC immune landscape, we conducted a comprehensive single-cell analysis of HPV16+ and HPV33+ primary tumors and metastatic lymph nodes. We used single-cell analysis with encoded peptide-human leukocyte antigen (HLA) tetramers to analyze HPV16+ and HPV33+ OPSCC tumors, characterizing the ex vivo cellular responses to HPV-derived antigens presented in major Class I and Class II HLA alleles.ResultsWe identified robust cytotoxic T-cell responses to HPV16 proteins E1 and E2 that were shared across multiple patients, particularly in HLA-A*01:01 and HLA-B*08:01. Responses to E2 were associated with loss of E2 expression in at least one tumor, indicating the functional capacity of these E2-recognizing T cells and many of these interactions validated in a functional assay. Conversely, cellular responses to E6 and E7 were limited in quantity and cytotoxic capacity, and tumor E6 and E7 expression persisted.ConclusionsThese data highlight antigenicity beyond HPV16 E6 and E7 and nominate candidates for antigen-directed therapies.