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Uveal melanoma is a rare intraocular tumour, with metastatic spread observed in up to 50% of patients, most often in the liver. Therapeutic options for metastatic patients are very limited, outcomes dismal and the survival time short once metastatic disease is diagnosed. The factors underlying metastatic disease remain poorly understood. The immune system has many pathways that can be used to attack 'invaders', but as patients with an ocular malignancy often die from metastases, the pathways are not effective in this disease. We have studied the presence of immune cells (macrophages and different types of T lymphocytes) in uveal melanoma, and in a murine ocular tumour model using B16 tumor cells grown in the eyes of young and old mice. Tumour growth in mice was also assessed after macrophage depletion. Two types of uveal melanoma were identified: those with a complex infiltrate consisting of macrophages, CD3, CD4, and CD8 lymphocytes, and those without. An inflammatory phenotype was associated with a specific chromosome aberration, loss of one chromosome 3 (monosomy 3). T cells with a suppressive phenotype were found in the tumors with an inflammatory infiltrate. Experimental mouse work showed that macrophages may play a role in intra-ocular tumor growth, especially in old mice.We concluded that uveal melanomas with the worst prognosis contain many macrophages and lymphocytes, including immuno-suppressive T cells. Macrophages may help to stimulate tumor growth, not inhibit it. Immune-targeted vaccines may provide a means to overcome the negative effects of immune suppressor cells. Developing therapies to influence macrophage behaviour in uveal melanoma (and other tumours) could also provide treatment options for these patients.
Martine J. Jager is a Professor of Ophthalmology at Leiden University, The Netherlands. She received her MD degree and PhD in immunology from Leiden University, did her residency in Ophthalmology at the University of Amsterdam, and a research and clinical Cornea and ocular surface disease fellowship at the Bascom Palmer Eye Institute in Miami. She is a frequent visitor at the Schepens Eye Research institute, Boston, where she holds a position as adjunct scientist.. Her research interests are immunology of corneal surface disorders and uveal melanoma, on which subjects she has published over 200 peer-reviewed papers as well as over 20 book chapters. She mentors medical students (now 100) and postdoctoral fellows (over 20), in the Netherlands as well as abroad. One of her self-appointed jobs is helping students to gain experience by studying in another country. She has lectured worldwide, and has been principal investigator on numerous grants dealing with the development and immunology of uveal melanoma. Many projects involve international collaborations. She is currently involved in two Horizon2020 projects, one on corneal regeneration, the other on on developing a therapy for uveal melanoma. Prof. Jager has served as President of the Association for Research in Vision and Ophthalmology (ARVO), is President-elect of the International Society of Ocular Oncology (ISOO), and a member of the Advisory Board of the International Council of Ophthalmology. In 2011, she was elected member of the Academia Ophthalmologica Internationalis.