Exploring CD8+ T cell-LCH-cell Interactions in Langerhans cell histiocytosis: A Three Center Study
Leiden University Medical Center, Leiden, Netherlands
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Langerhans Cell Histiocytosis (LCH) is a rare disease which typically presents itself as (chronically) inflamed tissue abnormalities which develop at one or several locations. While the majority of patients is successfully treated, some patients develop new lesions in time despite adequate treatment. In more than 50% of all cases, LCH lesions contain somatically mutated LCH-cells. While some studies focus on unravelling the full palette of genetic mutations which drive the formation of aberrantly differentiated LCH-cells, our project aims at understanding the molecular basis of the crosstalk between mutated LCH-cells and CD8+ T cells; the latter cells are often found in close proximity of LCH-cells (Figure 1) and are key for the recognition, elimination and prevention of new outgrowth of tumor cells in many different types of cancer. The presence of the BRAFV600E mutation seems to increase the risk of LCH reactivation [ML Berres J Exp Med 2014]. In this study, we propose to analyse in a large combined Canadian-Dutch LCH patient cohort how reactivation rates are affected by the patient’s mutation status, degree of infiltration of the lesion by CD8+ T cells and Human Leukocyte Antigen (HLA) profile. When this analysis is completed we will have a set of immune markers which are associated with a high risk of LCH reactivation. This information could be incorporated in future new studies initiated by the international Histiocyte Society wherein the results of new and existing therapeutic protocols are compared.