Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment.
J Immunother Cancer
; 11(3)2023 03.
Article
en En
| MEDLINE
| ID: mdl-36990508
ABSTRACT
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*0101 and HLA-B*0801. 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Orofaríngeas
/
Infecciones por Papillomavirus
/
Neoplasias de Cabeza y Cuello
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos