Yujun Dong, MD
JI 研究项目: 癌症和精准医学
Despite the recent development of novel drugs and therapeutic strategies, Multiple myeloma (MM) remains an incurable disease, and most patients relapse even after allogeneic hematopoietic stem cell transplantations (allo-
HSCT). Available data showed that immune check-point inhibitors are not as effective in MM as in Hodgkin Lymphoma, and immune evasion of myeloma cells against cellular immunity may be an important factor to explain this refractoriness. However, the mechanism of immune evasion in myeloma cells has not been elucidated. ER associated degradation (ERAD) complexes are important protein quality control systems to ensure the proper processing, folding and assembly of plasma membrane proteins including cell surface
antigens and antigen presentation complexes. Our preliminary data showed that the key molecule in Hrd1 ERAD, Sel1L, was expressed in myeloma cell lines and primary MM samples. Furthermore, the cell surface level of peptide-HLA complex (pHLA) on human MM cell lines was significantly altered after Sel1L knockdown. Thus, we hypothesize that Sel1L/Hrd1ERAD may be involved in antigen processing and presentation in myeloma cells, and modulating ERAD might be a new strategy to overcome the immune evasion of MM. The proposed studies will allow us to develop productive collaborations to identify mechanisms of immune evasion in MM, and develop new strategies to enhance response of myeloma cells to immunotherapies.