We will stduy a subtype of T cells, namely the natural killer (NKT) cells. These cells have features of both innate and adaptive immunity, hence they combine features of T cells and NK cells, for example through expression of NK receptors. However their activity is impaired in MM. In this project we aim to understand if and how NKT cells are cytotoxic against MM cells and whether we can use them as therapeutic tools by reactivating their functionality by using the prototype ligand alpha-galactosyl ceramide or altered glycolipids. This will be studied in patient samples and in the preclinical 5TMM mouse model of MM. Furthermore we will examine the effects of the immunomodulatory drug lenalidomide on NKT function to determine the ability and mechanism(s) of reversing NKT cell dysfunction in MM. This project is a collaboration of 2 well established, complementary centers, each with an excellent track record in their field, and should enhance our understanding of the dysfunctionality of the immune system in MM and provide new targets for treatment