Hist-P-02 - CD74 overexpression in cutaneous T-cell lymphoma and its inhibition as a potential therapeutic approach

Abstract

Cutaneous T-cell lymphomas form a heterogeneous group of non-Hodgkin lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. CD74 is a type II membrane glycoprotein that plays an important role in MHC class II antigen presentation. It is expressed by a number of immune cells, including B cells and macrophages. CD74 conveys proliferative and provital signals. This can lead to procarcinogenic effects and thus increase the survival of malignant cells. So far, as far as is known, neither the analysis of CD74 expression nor a therapeutic approach via CD74 blockade in cutaneous T-cell lymphomas has been described. In the presented study, CD74 expression in cutaneous T-cell lymphomas (CTCL), including subentities, and its association with clinical features were analyzed. Here, we demonstrate by quantitative RT-PCR, Western blotting, FACS analyzes and immunohistochemistry in CTCL cell lines and primary patient samples that CD74 is highly overexpressed in tumor cells. Moreover, treatment with a specific CD74 inhibitor blocks cell viability. These new data provide a promising rationale for using CD74 inhibition as a therapeutic modality in CTCL.