Multiple myeloma (MM) is a progressive monoclonal B cell malignancy, for which 
survival and progression largely relies on the crosstalk of tumor cells with the 
bone marrow (BM) microenvironment, inducing immune escape, angiogenesis, bone 
destruction and drug resistance. Despite great therapeutic advances, most of the 
MM patients still relapse and remain incurable. Over the past years, 
immunotherapy has emerged as a new field in cancer therapy. Here, the immune 
cells of the patients themselves are activated to target the tumor cells. In MM, 
several effector cells of the immune system are present in the BM 
microenvironment; unfortunately, they are mostly all functionally impaired. In 
this review, we focus on the role of innate-like T cells in MM, particularly 
CD1d- and MR1- restricted T cells such as respectively invariant natural killer 
T (iNKT) cells and mucosal associated invariant T (MAIT) cells. These cells have 
the capacity upon activation to rapidly release copious amounts of cytokines 
affecting a wide range of innate and adaptive immune responses, and could 
therefore play a key protective role in anti-tumor immunity. We describe recent 
observations with regard to functional exhaustion of iNKT and MAIT cells in MM 
pathology and discuss the potential application of checkpoint inhibition as an 
attractive target for prolonged activation of these immunomodulatory T cells in 
the treatment of MM.