High-dimensional single-cell analysis of the immune response in multiple myeloma and profiling of the T cell repertoire in response to immunomodulatory treatment

Abstract

Abstract Multiple myeloma is a largely incurable malignancy of plasma cells in the bone marrow. The standard of care for this disease has increasingly included the use of immunomodulatory drugs such as thalidomide and its derivatives. However, high-dimensional analysis of the immune response in multiple myeloma tumors and the resultant response to immunomodulatory treatment is lacking. Here, we present a single-cell multi-omic analysis of the immune response in refractory multiple myeloma patient tumors including profiling of CD8+ T cell antigen specificities. We also analyze changes in the T cell repertoire and gene expression following treatment of pomalidomide. We observe a contraction of the repertoire that includes the expansion of select clones within the repertoire. These results provide a clearer map of the immune response in multiple myeloma and how patients respond to immunomodulatory treatment. Supported by grants from CRI Lloyd J. Old STAR Program and NIH R33 IMAT 2018