Universität zu Köln

Peil, Jennifer (2025). Importance of dendritic cells in pathogenesis and therapy of conjunctival melanoma. PhD thesis, Universität zu Köln.

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Abstract

Conjunctival melanoma is a very rare malignant tumor, which occurs in less than 5 % of ocular melanomas. Because of the high recurrence rate of CM, current therapy options are insufficient and, for advanced CM, no standardized therapy is available. The immunological principles, especially the composition of dendritic cell subsets and their functions, are almost completely unknown in CM. DCs are antigen-presenting cells and link the innate and the adaptive immune system. In this dissertation, we investigated the immune cell composition in the physiological conjunctiva, CM and in the draining lymph nodes, the lymph- and hemangiogenic profile and the effect of local injection of non-activated classical DCs on survival, metastases and tumor progression in vivo in immunocompetent C57BL/6N mice using a HGF-Cdk4R24C CM model. DCs can be subclassified into cDC₁, cDC₂, plasmacytoid and monocyte derived DCs. Subclassification showed that CD103- cDC₂ are the most common DC subset in healthy conjunctiva and that CD103- cDC₂, CD103+ cDC₁, moDCs and pDCs are significantly increased in CM. A local injection of non-activated cDC₂ showed neither positive nor negative effects. Furthermore, the angiogenic factors expressed by cDCs and tumor cells were verified in vitro and identified Osteopontin as the most relevant cytokine expressed by the tumor cells, which actually interacts with DCs. We evaluated a combined therapy strategy for CM by subconjunctival OPN blockade and activated cDC vaccination. The combined therapy slowed down tumor progression and inhibited tumor growth completely in 35 % of cases. To better understand the mode of action of the OPN blockade, tumor cells and cDCs, the effect on blood- and lymphatic endothelial cells was studied in co-culture with the supernatant of DCs and tumor cells in combination with an OPN blocking antibody or additional OPN protein in vitro. The results of this thesis will help to get a better understanding of the immunological principles in the development of CM and the influence of the tumor microenvironment on the activity of DCs and on blood- and lymhangiogenesis.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Peil, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-750107
Date:	2025
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Medicine > Augenheilkunde
Subjects:	Life sciences Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Dendritic cells English Conjunctival melanoma English Osteopontin English Immune system English Mouse model English Ocular melanoma English Angiogenesis English Metastasis English
Date of oral exam:	19 December 2024
Referee:	Name Academic Title Ullrich, Roland Prof. Dr. Dr. Eming, Sabine Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/75010