Immunosurveillance in multiple myeloma: Mechanisms, challenges, and therapeutic implications

Multiple myeloma (MM) is a frequent cancer involving uncontrolled plasma cell growth in the bone marrow, causing bone damage, kidney issues and anemia. The immune system's capacity to recognize and eliminate malignant cells is essential in controlling MM progression. Through coordinated actions of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, immune surveillance mechanisms work to keep early disease stages like monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) in check. However, as MM advances, the immune landscape undergoes significant changes, impairing the functionality of key immune cells. Indeed, the bone marrow microenvironment in MM fosters immune dysfunction through inflammatory networks and the presence of regulatory cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). This enables myeloma cells to evade immune detection, presenting a substantial barrier to effective treatment. Despite the remarkable clinical efficacy of novel immunotherapies such as CAR T-cells and bispecific antibodies, many patients eventually experience relapse. Targeting both the malignant cells and the immunosuppressive elements within MM microenvironment may therefore be key to achieving durable responses and potentially curing MM.