Professor Dr Martine Jager

Research Priorities: Ocular tumours, uveal melanomas, choroid melanomas, role of the immune system and genetics in ocular tumours, corneal transplantations

Martine Jäger is a Dutch ophthalmologist and immunologist. She researches ocular tumours and the immune system, focusing on two aspects: improving the survival rate of patients with ocular tumours by strengthening the immune response, and improving treatment for patients with corneal transplants by weakening the immune response. She also advocates for stronger international cooperation to improve ocular research and to achieve improved treatment worldwide for people with eye issues.

Uveal melanoma is the most common malignant cancer disease of the eye in adults. Although treatment for the primary tumour is well developed, hardly any treatment is effective for metastases. Martine Jager and her team have contributed to discovering why some uveal melanomas develop deadly metastases and others do not. For this purpose she combined clinical data from a database of cell cultures and murine investigations. The results help to involve patients in studies for neo-adjuvant therapies or the early detection of metastases. The dataset from her department in Leiden has also helped develop the grouping for ocular cancer of the American Joint Committee of Cancer.

Martine Jager uses insights on the immunological and biochemical characteristics of uveal melanoma in order to develop effective treatments for metastases. With her Leiden group she discovered that uveal melanoma can be divided into two groups based on the mRNA expression pattern and that a high expression of HLA antigens is related to a bad prognosis. 

Furthermore, Martine Jager was the first to discover that a certain genetic change in the tumour (Chromosome 3 loss) is related to an increased infiltration with monocytes and lymphocytes, and that this is a case of immunosuppression. However, when T cells are separated from the tumour cells, they are very well able to respond against the tumour. This is where the new therapies come in. The Leiden mRNA dataset was also part of the study that identified PRAME (Preferentially Expressed Antigen in Melanoma) as a prognostic marker, because PRAME is almost exclusively formed by cancer cells. For the work on the new treatment, the group worked with the company Aura to combine a tumour-directed laser treatment with immune checkpoint inhibitors in a murine model. The team discovered that this treatment helps reject tumours elsewhere in the body. 

North-western Europe is a particular region for uveal melanoma: People with blue eyes are more susceptible to developing this type of malignant disease. The responsible genes are related to pigmentation, and at least one of them (HERC2) is not only relevant to eye colour but is also related to an increased risk of developing a malignant uveal melanoma (with loss of one chromosome 3/BAP1 mutation). In other work Martine Jager researched the precise role of HERC2 in the occurrence of highly malignant tumours. 

Another research focus is on transplantation medicine. While in tumour immunology the goal is to reject the tumour, the opposite is true in this case: reducing the rejection of the transplant. Patients with diseases of the anterior eye segment, however, are at high risk of corneal transplant rejection. Jager’s group developed an artificial cornea in collaboration with other European research groups. 

Many stem cell transplants are also carried out at the LUMC and some patients suffer from a severe ocular Graft-versus-Host-Disease (GvHD). Martine Jager was part of working to improve the quality of life of patients with GvHD and severe autoimmune diseases and she continues to research the role of antigens in the transplantation of different tissues such as the cornea and the retinal pigment epithelium. The most important objective of her research is to develop new treatments and help patients.