Objective: Few studies have focused on investigating resistance mechanisms in myeloma immunotherapy. This study aimed to explore the relevant factor involved in the resistance of Elotuzumab and lenalidomide.
Methods: Cell models which are resistant to Elotuzumab and lenalidomide were constructed; different expression genes in U266/WT (UW) and resistant UR, UE, and URE cells were detected by using gene expression microarray. RT-qPCR validated CCL20 mRNA expression of four cell lines and patient samples; bioinformatics analysis of CCL20 expressions in NDMM and RRMM; ELISA detected the presence of CCL20 in the plasma of MM patients; constructed UR mouse xenograft model to explore whether or not CCL20 reverse lenalidomide treatment in vivo.
Results: Cell models which are resistant to Elotuzumab and lenalidomide (UR, UE, URE) were successfully constructed. CCL20 gene expression decreased in resistant myeloma cell lines and RRMM patients. Furthermore, RRMM patients were found to have lower levels of CCL20 protein in their plasma compared to NDMM. CCL20 increase the sensitivity of drug-resistant myeloma cells to immunomodulatory drugs both in vivo and in vitro.
Conclusion: The expression of CCL20 was decreased in lenalidomide and Elotuzumab resistant U266 cells and in RRMM patients. CCL20 could therefore possibly increase the sensitivity of lenalidomide and Elotuzumab.
Keywords: CCL20, elotuzumab, lenalidomide, drug resistance, multiple myeloma