Characterization of tumor-infiltrating B-cells in cutaneous T-cell lymphoma

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The overall aim of this project is the characterization of tumor-infiltrating B-cells in cutaneous T-cell lymphoma.B-cells are conventionally regarded as antibody-producing cells of the adaptive immune response. However, it has been known for some years that B-cells can also act as professional antigen-presenting cells and immunoregulatory cells and, as such, can contribute significantly to the pathogenesis of autoimmune diseases and cancer.Cutaneous T-cell lymphomas (CTCL) are a highly intersting cancer entity from a tumor-immunological viewpoint because they are immunogenic and can be monitored clinically and serially biopsied. In early stages, CTCL hardly affect the life expectancy of the affected individuals. However, in some cases and associated with certain CTCL subtypes, a rapid, aggressive course can occur already in the early phase of the disease, for which the reasons are not fully understood. In close cooperation with our dermatological colleagues (Dr. Schlaak, Prof. Stadler), we have in our preliminary work observed that the tumor tissues of aggressive and advanced CTCL show strong B-cell infiltrates, which correlated with por survival. In addition, we observed that local B-cell depletion by the CD20 antibody rituximab in a patient with refractory CTCL and demonstrably strong B-cell infiltrate resulted in a complete and sustained local tumor remission. However, the precise characteristics of CTCL-associated B-cells and their function are still largely unknown. In this project, we therefore aim to characterize CTCL-infiltrating B-cells in detail using phenotypical and functional ex vivo and in vivo (mouse) experiments. The results could help develop a novel immunotherapeutic treatment option for advanced and standard therapy refractory CTCL cases, which does not directly act on the malignant cells but rather shapes the tumor immune environment.