Tbet-positive regulatory T cells accumulate in oropharyngeal cancers with ongoing tumor-specific type 1 T cell responses

Regulatory T cells (Tregs) may comprise different subsets allowing them to efficiently suppress different types of effector T cells. In this study, we show that high numbers of both conventional and Tbet co-expressing Foxp3 Tregs accumulate in human papilloma virus (HPV)-driven oropharyngeal squamou...

Full description

Saved in:

Bibliographic Details
Published in:	Journal for immunotherapy of cancer Vol. 7; no. 1; p. 14
Main Authors:	Santegoets, S J, Duurland, C L, Jordanova, E S, van Ham, J J, Ehsan, I, van Egmond, S L, Welters, M J P, van der Burg, S H
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 18-01-2019 BMJ Publishing Group LTD BioMed Central BMJ Publishing Group
Subjects:	Aged Aged, 80 and over Antigens Cancer Carcinoma Care and treatment Cloning Cytokines DNA methylation Enzymes Female Flow cytometry Forkhead Transcription Factors - immunology Foxp3 Genes Head & neck cancer Head and neck cancer HPV Human papillomavirus Humans Immunotherapy Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Male Middle Aged Oropharyngeal Neoplasms - etiology Oropharyngeal Neoplasms - immunology Papillomavirus infections Papillomavirus Infections - complications Papillomavirus Infections - immunology Patients Pharyngeal cancer Squamous cell carcinoma Survival analysis T cells T-Box Domain Proteins - immunology T-Lymphocytes, Regulatory - immunology Throat cancer Transcription factors Tumor microenvironment Tumors Type 1 immunity Uterine Cervical Neoplasms - etiology Uterine Cervical Neoplasms - immunology Head and neck cancer Tumor microenvironment Foxp3 Type 1 immunity HPV
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Regulatory T cells (Tregs) may comprise different subsets allowing them to efficiently suppress different types of effector T cells. In this study, we show that high numbers of both conventional and Tbet co-expressing Foxp3 Tregs accumulate in human papilloma virus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC). The infiltration of Tbet+ Foxp3+ Tregs was strongly correlated with a concomitant tumor-specific and conventional type 1-oriented intratumoral T cell infiltrate. Both conventional CD4+CD25+CD127-Foxp3 Tregs and their Tbet counterparts exhibited an activated phenotype, co-expressed high levels of CTLA4 and Helios and exhibited a maximally demethylated Foxp3 gene locus TSDR, indicating their full capacity to impede a type 1 effector T cell response. Interestingly, while the prognostic value of conventional Tregs was neutral, a high intratumoral frequency of Tbet+ Tregs was associated with prolonged disease-specific survival, most likely because their presence reflected high numbers of effector T cells. The presence of these Tbet+ Tregs may in part explain why a dense type 1-oriented immune infiltrate in OPSCC is not enough to fully control tumor growth.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23
ISSN:	2051-1426 2051-1426
DOI:	10.1186/s40425-019-0497-0