Profiling HPV-16-specific T cell responses reveals broad antigen reactivities in oropharyngeal cancer patients.
Antigens, Neoplasm
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Case-Control Studies
Female
Human papillomavirus 16
/ immunology
Humans
Male
Middle Aged
Oropharyngeal Neoplasms
/ immunology
Papillomavirus Infections
/ immunology
T-Lymphocytes
/ immunology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
05 10 2020
05 10 2020
Historique:
received:
03
03
2020
revised:
05
05
2020
accepted:
15
06
2020
entrez:
28
7
2020
pubmed:
28
7
2020
medline:
11
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32716518
pii: 151975
doi: 10.1084/jem.20200389
pmc: PMC7537390
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 Bhatt et al.
Déclaration de conflit d'intérêts
Disclosures: B. Aftab reported "other" from Atara Biotherapeutics. during the conduct of the study; "other" from Atara Biotherapeutics outside the submitted work; and is an employee and has stock in Atara Biotherapeutics. C. Smith reported personal fees and grants from Atara Biotherapeutics during the conduct of the study. S. Porceddu reported personal fees from UpToDate and MerckSerono outside the submitted work. R. Khanna reported grants from Atara Biotherapeutics during the conduct of the study; personal fees from Atara Biotherapeutics outside the submitted work; had a patent to HPV immunotherapy pending; and is on the scientific advisory board of Atara Biotherapeutics. No other disclosures were reported.
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