Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session

259 - Inflamed human oropharyngeal cancers with ongoing tumor-specific T cell responses comprise a different type of immune suppressive T cells


14 Dec 2018


Poster Display session


Saskia Santegoets


Annals of Oncology (2018) 29 (suppl_10): x11-x16. 10.1093/annonc/mdy485


S.J. Santegoets1, C.L. Duurland1, E.S. Jordanova2, V.J. van Ham1, I. Ehsan1, M.J. Welters1, S.H. van der Burg1

Author affiliations

  • 1 Medical Oncology, Leids Universitair Medisch Centrum (LUMC), 2333 ZA - Leiden/NL
  • 2 Pathology, Leids Universitair Medisch Centrum (LUMC), 2333 ZA - Leiden/NL


Abstract 259


Recent studies have shown that for optimal immune suppression regulatory T cells (Tregs) are required to adopt a transcriptional profile similar to that of the type of T cells they aim to suppress. For instance, Foxp3+ Tregs upregulate the Th1-associated transcription factor Tbet to control a type 1 cytokine-mediated inflammatory response in order to prevent unwanted tissue destruction and immunopathology. However, little is known about the existence and function of such Treg cells in cancer patients.


To study the presence and potential impact of Tbet-expressing Foxp3+ (Foxp3+Tbet+) Tregs in human cancer, we applied three-color immunofluorescence staining and 12-parameter flow cytometry on the tumor microenvironment (TME) of human papilloma virus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) patients.


Our data revealed that Foxp3+Tbet+ Tregs accumulate and dominate in the tumor cell nests of patients with a concomitant HPV-specific and type 1-oriented intratumoral T cell infiltrate. Moreover, these CD4+CD25+CD127–Foxp3+Tbet+ Tregs exhibited an activated phenotype and co-expressed high levels of CTLA4 and Helios. Assessment of the methylation status of the FoxP3 gene locus TSDR of flow cytometry-sorted Foxp3+Tbet+ and Foxp3+Tbet - Tregs revealed that it was maximally demethylated, indicating that these Tregs have the full capacity to suppress immune cells. Interestingly, OPSCC patients with high intratumoral frequencies of Foxp3+Tbet+ Tregs, but not Foxp3+Tbet– Tregs, displayed prolonged disease-specific survival, suggesting that the presence of Foxp3+Tbet+ Tregs is a reflection of a strong and clinically favorable local tumor-specific type 1 immune response.


In conclusion, bona fide Foxp3+Tbet+ regulatory T cells accumulate in HPV16-driven tumors that are highly infiltrated with type 1 tumor-specific T cells, at levels enough to impede full spontaneous immune-mediated tumor control.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Sjoerd H. van der Burg.


The Dutch Cancer Society.


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.