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

这个项目的总体目的是表征肿瘤浸润的b细胞在皮肤t细胞淋巴瘤。b细胞通常被认为是适应性免疫反应的抗体产生细胞。然而，多年来人们已经知道b细胞也可以作为专业抗原提呈细胞和免疫调节细胞，因此，b细胞在自身免疫性疾病和癌症的发病机制中起着重要作用。从肿瘤免疫学的角度来看，皮肤t细胞淋巴瘤（CTCL）是一种非常有趣的癌症实体，因为它们具有免疫原性，可以在临床监测和连续活检。在早期阶段，CTCL几乎不影响患者的预期寿命。然而，在某些病例和与某些CTCL亚型相关的病例中，在疾病的早期阶段就可能发生快速的侵袭性病程，其原因尚不完全清楚。在与皮肤科同事（Schlaak博士，Stadler教授）的密切合作下，我们在前期工作中观察到侵袭性和晚期CTCL的肿瘤组织表现出强烈的b细胞浸润，这与生存率低有关。此外，我们观察到，在难治性CTCL患者中，CD20抗体利妥昔单抗局部b细胞耗竭和明显强b细胞浸润导致局部肿瘤完全和持续缓解。然而，ctcl相关b细胞的确切特征及其功能在很大程度上仍然未知。因此，在这个项目中，我们的目标是通过体外和体内（小鼠）实验来详细描述ctcl浸润b细胞的表型和功能。这些结果可能有助于为晚期和标准治疗难治性CTCL病例开发一种新的免疫治疗选择，这种治疗不直接作用于恶性细胞，而是塑造肿瘤免疫环境。

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.