- Tjin Esther P. M., Konijnenberg Debby, Krebbers Gabrielle, Mallo Henk, Drijfhout Jan W., Franken Kees L. M. C., van der Horst Chantal M. A. M., Bos Jan D., Nieweg Omgo E., Kroon Bin B. R., Haanen John B. A. G., Melief Cornelis J. M., Vyth-Dreese Florry A., Luiten Rosalie M. T-cell immune function in tumor, skin, and peripheral blood of advanced stage melanoma patients: implications for immunotherapy Clinical cancer research 2011;17 (17):5736-5747 [PubMed]
Prof. PhD R.M. Luiten (Pigment cell disorders of the skin)
Luiten's research team is specialized in the immunopathogenesis and treatment of pigment cell disorders of the skin, including vitiligo and melanoma. Luiten's research has clearly established a positive relation between vitiligo and melanoma regression, by showing that 1) vitiligo patients have a three-fold decreased life-time risk of developing melanoma , 2) vitiligo is an autoimmunity against melanocytes in the skin, leading to loss of skin pigmentation, 3) melanoma patients who develop vitiligo, referred to as melanoma-associated leucoderma or vitiligo (MAL), have immunity reactive with both melanocytes and melanoma cells, 4) the appearance of MAL in melanoma patients is associated with favorable clinical outcome (progression free- and overall survival), and 5) vitiligo-inducing compound monobenzone combined with imiquimod and/or CpG induces anti-melanoma immunity and suppresses melanoma growth in mice and patients. This highlights vitiligo as a favorable sign for melanoma patients and the importance of its mechanism of action for melanoma treatment. The group has developed a new melanoma therapy consisting of monobenzone and immune stimulation (patent granted, preclinical and clinical proof-of-concept obtained). Their investigator-initiated clinical trial at the NKI-AVL shows local clinical responses of skin metastases and successful induction of anti-melanoma immunity in most patients. This therapy is developed further clinically. New projects include biomarker research for response of melanoma patients to immune checkpoint inhibitors, targeting of melanoma cell heterogeneity by vaccination immunotherapy and diagnosis and treatment of lentigo maligna. Vitiligo clinical research aims at improving skin suspension transplantation therapy and the development of scoring systems for vitiligo disease activity. Biomarkers for the differential diagnosis of vitiligo and melanoma-associated vitiligo are studied, applicable in preventing immunesuppressive therapy in vitiligo patients with an undiagnosed melanoma. Luiten's group joined forces of the NFU expertise center on Pigment Disorders (AMC) with the skin tissue engineering expertise of prof Gibbs (VUMC), to apply this technology in vitiligo and melanoma immunotherapy research.
PhD W. Ouwerkerk
BEng S. Chielie
BEng G. Krebbers
N.O.P. van Uden