The yin–yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma

Abstract

Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules.

Determination of the target of monoclonal immunoglobulins: a novel diagnostic tool for individualized MGUS therapy, and prevention and therapy of smoldering and multiple myeloma

“…Clearly, anti-viral therapy should be prescribed as early as possible in the development of clonal gammopathies linked to viruses, ideally at the MGUS stage, though benefits in terms of improved overall survival were also demonstrated at the MM stage (22-24). For patients with a monoclonal Ig reactive against a self-antigen, knowing that autoimmunity initiated the monoclonal gammopathy should help understand the immune environment that leads to MM and adapt treatment (61). Prospective studies in large cohorts of patients are necessary to validate the prognostic and therapeutic interest of each of the infectious or auto-antigen targets of monoclonal Igs.…”