Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment
Background High-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...
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| Language: | English |
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BMJ Publishing Group
2023-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/3/e006721.full |
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| author | Christine McInnis Lakshmi Srinivasan Anthony J Coyle Shilpa Bhatia Glenn J Hanna Ann Marie Egloff Brinda Vijaykumar Qiaomu Tian Yanbo Sun Del Leistritz-Edwards Charles T Quinn Ravi Uppaluri Daniel C Pregibon |
| author_facet | Christine McInnis Lakshmi Srinivasan Anthony J Coyle Shilpa Bhatia Glenn J Hanna Ann Marie Egloff Brinda Vijaykumar Qiaomu Tian Yanbo Sun Del Leistritz-Edwards Charles T Quinn Ravi Uppaluri Daniel C Pregibon |
| author_sort | Christine McInnis |
| collection | DOAJ |
| description | Background High-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.Methods To 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.Results We 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.Conclusions These data highlight antigenicity beyond HPV16 E6 and E7 and nominate candidates for antigen-directed therapies. |
| format | Article |
| id | doaj-art-8563618d2440465aa2a5fd3a1eb10376 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-8563618d2440465aa2a5fd3a1eb103762025-02-10T11:35:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-03-0111310.1136/jitc-2023-006721Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironmentChristine McInnis0Lakshmi Srinivasan1Anthony J Coyle2Shilpa Bhatia3Glenn J Hanna4Ann Marie Egloff5Brinda Vijaykumar6Qiaomu Tian7Yanbo Sun8Del Leistritz-Edwards9Charles T Quinn10Ravi Uppaluri11Daniel C Pregibon12Repertoire Immune Medicines, Cambridge, Massachusetts, USA10 Pediatrics, Children`s Hospital of Philadelphia, Philadelphia, Pennsylvania, USARepertoire Immune Medicines, Cambridge, Massachusetts, USARepertoire Immune Medicines, Cambridge, Massachusetts, USA3Dana-Farber Cancer Institute, Boston, MA, USADivision of Otolaryngology-Head and Neck Surgery, Brigham and Women`s Hospital, Boston, Massachusetts, USARepertoire Immune Medicines, Cambridge, Massachusetts, USARepertoire Immune Medicines, Cambridge, Massachusetts, USARepertoire Immune Medicines, Cambridge, Massachusetts, USARepertoire Immune Medicines, Cambridge, Massachusetts, USACenter for Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USADivision of Otolaryngology-Head and Neck Surgery, Brigham and Women`s Hospital, Boston, Massachusetts, USARepertoire Immune Medicines, Cambridge, Massachusetts, USABackground High-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.Methods To 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.Results We 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.Conclusions These data highlight antigenicity beyond HPV16 E6 and E7 and nominate candidates for antigen-directed therapies.https://jitc.bmj.com/content/11/3/e006721.full |
| spellingShingle | Christine McInnis Lakshmi Srinivasan Anthony J Coyle Shilpa Bhatia Glenn J Hanna Ann Marie Egloff Brinda Vijaykumar Qiaomu Tian Yanbo Sun Del Leistritz-Edwards Charles T Quinn Ravi Uppaluri Daniel C Pregibon Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment Journal for ImmunoTherapy of Cancer |
| title | Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment |
| title_full | Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment |
| title_fullStr | Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment |
| title_full_unstemmed | Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment |
| title_short | Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment |
| title_sort | identification of hpv16 e1 and e2 specific t cells in the oropharyngeal cancer tumor microenvironment |
| url | https://jitc.bmj.com/content/11/3/e006721.full |
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