Impact of monocyte- and macrophage- derived CCL22 on endometrial cancer

Aim Endometrial cancer (EC) is described as a highly immunogenic tumor disease. The chemokine CCL22, secreted i.a. by macrophages and activated monocytes, has been reported to play an important role in attracting several immune cell types und thus supporting cancer immune evasion by creating an immunosuppressive microenvironment. But few results are published concerning endometrial cancer (EC) in this context.

Methods and Results Immunohistochemical staining of 300 EC patients demonstrated that CCL22 expression in tumor cells, as well as in strongly positive, isolated cells in the tumor-distant myometrial area, is a predictor of a longer overall survival (p=0.011 and p=0.042). On the other hand, a positive staining in stromal areas close to the tumor tends to result in a lower overall survival rate (p=0.056), as expected with tumor-associated macrophages (TAMS) being associated with cancer progression and poor prognosis in EC. Further characterization of the relevant immune cell-subtypes by double immunofluorescence is planned. Additional experiments shall reveal the interactivity between peripheral blood mononuclear cells and monocyte/macrophage-subpopulation regarding CCL22 secretion in coculture with two EC tumor cell lines (Ishikawa+ and RL95-2).

Conclusion In summary our findings will be the first investigation in EC cell culture to detect the importance of monocytes and macrophages in CCL22 dependent cancer immune evasion and could provide hints for CCL22 as a potential predictor for tumor prognosis and targeted therapy in EC.

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