Inflammation and immunomodulation in uveal melanoma

Ly, L.V. (2011)

Doctoral Thesis

This thesis describes the role of the immune system as an important phenomenon in the most frequently occurring form of eye cancer in adults, namely in uveal melanoma. We show that the immune system can be the cause of the tumor, and also plays a role in the development of a tumor, and may be an entry for therapy. In the first chapters of this thesis, we describe the phenomenon of "an inflammatory phenotype" in uveal melanoma. It appears that when this type of cancer shows more inflammation, the survival of patients decreases. A possible explanation for this observation is that one of the key players among the immune cells, the macrophage, plays an essential role in intra-ocular tumor growth. We demonstrate this in patient material, but also in experimental studies; we are able to inhibit tumor growth when we modulate the presence of macrophages. In this thesis, we also show that the immune system can be used effectively to eradicate eye melanomas in experimental models. T cell vaccination in combination with monoclonal antibodies gave promising results for treating eye cancer. Further research has to be performed to translate this into the clinic.

• Eye cancer
• Uveal melanoma
• Macrophages
• M2-type macrophages
• Age
• T cell vaccination
• Adoptive transfer
• Inflammation
• Monosomy 3
• Monoclonal antibodies

• All authors: Ly, L.V.
• Supervisor: Luyten, G.P.M.
• Co-supervisor: Jager, M.J.; Hall, T. van
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2011-04-12
• ISBN (print): 9789081692410