The immune system in multiple myeloma and precursor states: Lessons and implications for immunotherapy and interception

Abstract

Multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) are distinct disorders that likely originate in the setting of chronic immune activation. Evolution of these lesions is impacted by cross-talk with both innate and adaptive immune systems of the host. Harnessing the immune system may, therefore, be an attractive strategy to prevent clinical malignancy. While clinical MM is characterized by both regional and systemic immune suppression and paresis, immune-based approaches, particularly redirecting T cells have shown remarkable efficacy in MM patients. Optimal application and sequencing of these new immune therapies and their integration into clinical MM management may depend on the underlying immune status, in turn impacted by host, tumor, and environmental features. Immune therapies carry the potential to achieve durable unmaintained responses and cures in MM.

Fig 1.

Factors impacting tumor- and pathogen-specific immunity in MM Tumor and pathogen-specific immunity in MM is likely impacted by several factors that can be broadly classified as tumor, host, environment and therapy related factors.

Fig 2.

Major changes in T and myeloid composition between MGUS and myeloma Bone marrow in myeloma is characterized by greater enrichment of terminal effector T cells, along with immune suppressive myeloid cells and stromal inflammation.