Regulatory T-cells as a potential target to overcome immune evasion in endometrial cancer

Aim The infiltration of FoxP3-positive regulatory T-cells (Treg) is a mechanism of cancer immune evasion and associated with poor prognosis in many patients. Tregs are a Tcell subpopulation with immunosuppressive abilities, which are extensively attracted by the chemokine CCL22. We aim to investigate the impact of Treg on endometrial cancer (EC) and to assess whether the presence of CCL22 is associated with Treg infiltration.

Material and Methods A panel of 300 paraffin-embedded samples from patients with EC is stained for CCL22 and FoxP3. A correlation of the results with clinical parameters will be performed. This data will be supplemented by double immunofluorescence to characterise the CCL22 expressing cells and to analyse the interaction between Treg and macrophages. Furthermore, Treg-cells will be isolated from the peripheral blood of healthy volunteers and co-cultured with EC cell lines (Ishikawa and RL95-2), followed by functional assays to determine proliferation, viability and migration of the tumor cells. The effect of tumor cells on Treg will be further assessed by coculture experiments of peripheral blood mononuclear cells (PBMC) to investigate, if the number of FOXP3 positive-Treg within the PBMC increases, as shown for other tumor entities.

Results In progress.

Conclusion For advanced or recurrent cases of EC, new therapeutic options are needed. A very pronounced immunosuppressive tumor microenvironment with elevated Treg numbers can be a potential target to improve immune response and patient survival in EC and the depletion of Tregs may enhance the antitumor immunity.

Funding Funding programme by Ludwig-Maximilians-University (Förderprogramm für Forschung und Lehre)

Interessenkonflikt

Theresa M. Kolben is employed at Roche and holds stock of Roche. Alexander Burges has received advisory board an honoraria from AstraZeneca, Roche, and Tesaro. Fabian Trillsch declares Research support, advisory board, honoraria and travel expenses from AstraZeneca, Clovis, Medac, PharmaMar, Roche, Tesaro Sven Mahner has received Research support, advisory board, honoraria and travel expenses from AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, MSD, Novartis, Olympus, PharmaMar, Roche, Sensor Kinesis, Teva, Tesaro. Thomas Kolben has a relative employed at Roche and holds stock of Roche. All other authors declare that they have no conflict of interest.

Publication History

Article published online:
07 October 2020