CD200 is a potent new growth factor in Multiple Myeloma dependent on IGF1 receptor signaling

CD200 is an immune checkpoint aberrantly expressed in 70% of newly diagnosed patients with multiple myeloma (MM) and associated with a poor outcome. CD200 expression by tumor cells inhibits immune response through interaction with CD200R and participates in resistance to immune based therapies. However, its role in tumorigenesis remains poorly understood. In this study, we show that MM cells overexpressing CD200 present a significant proliferative advantage in serum free culture medium and clonogenic assays. The cell growth advantage mediated by CD200 in MM cells is dependent on the presence of IGF1R but independent on the presence of CD200R. Of interest, we reported that high expression of CD200 and IGF-1R is associated with a poor outcome in two independent cohorts of MM patients. Moreover, immuno-precipitation and mass spectrometry experiment identifies CD200 in the IGF1R-associated protein complex in association with AKT phosphorylation at Threonine 308 and activation. In conclusion, we demonstrate, for the first time, that CD200 supports myeloma cell growth through interaction with IGF-1R. Furthermore, combined approaches targeting CD200 and IGF-1R may provide new therapeutic avenues to target CD200 mediated cell growth function and its immunosuppressive functions associated with resistance to immune based therapies in MM.