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Poster Display session

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

Date

14 Dec 2018

Session

Poster Display session

Presenters

Saskia Santegoets

Citation

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

Authors

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
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Resources

Abstract 259

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Funding

The Dutch Cancer Society.

Disclosure

All authors have declared no conflicts of interest.

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