The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 5242
• Main Authors: Lagreca, Ivana, Riva, Giovanni, Nasillo, Vincenzo, Barozzi, Patrizia, Castelli, Ilaria, Basso, Sabrina, Bettelli, Francesca, Giusti, Davide, Cuoghi, Angela, Bresciani, Paola, Messerotti, Andrea, Gilioli, Andrea, Pioli, Valeria, Colasante, Corrado, Vallerini, Daniela, Paolini, Ambra, Maccaferri, Monica, Donatelli, Francesca, Forghieri, Fabio, Morselli, Monica, Colaci, Elisabetta, Leonardi, Giovanna, Marasca, Roberto, Potenza, Leonardo, Manfredini, Rossella, Tagliafico, Enrico, Trenti, Tommaso, Comoli, Patrizia, Luppi, Mario
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.05.2022; MDPI
• Subjects: Antigens; Benign monoclonal gammopathy; Bone diseases; Bone marrow; Cancer therapies; Cell proliferation; Chimeric antigen receptors; Cytokines; Cytotoxicity; Deregulation; Disease Progression; Humans; Immune system; Immunology; Immunopathogenesis; immunotherapy; Ligands; Lymphocytes; Lymphocytes T; Medical prognosis; MGUS; Monoclonal gammopathy; Monoclonal Gammopathy of Undetermined Significance - pathology; Multiple myeloma; Multiple Myeloma - pathology; Multiple Myeloma - therapy; Mutation; Paraproteinemias - therapy; Plasma; Plasma cells; Proteins; Review; Smoldering; Smoldering Multiple Myeloma; T cell immunity; T-Lymphocytes - pathology; Therapeutic applications; tumor microenvironment; Vascular endothelial growth factor; T cell immunity; multiple myeloma; tumor microenvironment; MGUS; plasma cells; immunotherapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23095242

Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.