One of the great advances in the field of cancer therapy in recent years is the emergence of
immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising
results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and
lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to
hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by
clonal proliferation of malignant plasma cells mainly in the bone marrow (BM). MM is associated with
both cellular and humoral immune deficiencies, indicating that the evolution of the disease from a precursor
state (monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM
(sMM)) is associated with an immunosuppressive milieu that fosters immune escape and tumor growth.
Despite significant advances in treatment, MM is mostly an incurable disease. Therefore, it is vital to
develop novel therapeutic agents that not only target the MM clone itself but also the MM immune microenvironment.
However, the complexity of the BM microenvironment and heterogeneity of tumor
cell clones make it a difficult task for developing appropriate immune therapies of MM. In this article,
we review the current knowledge of the interaction between malignant plasma cells and the bone marrow
immune microenvironment during disease progression.