Co-evolution of Immune Response in Multiple Myeloma: Implications for Immune Prevention

• Type of Material: Article
• Authors: Samuel S McCachren, Emory University; Kavita Dhodapkar, Emory University; Madhav Dhodapkar, Emory University
• Language: English
• Date: 2021-02-26
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2021 McCachren, Dhodapkar and Dhodapkar
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2021.632564
• Title of Journal or Parent Work: FRONTIERS IN IMMUNOLOGY
• Volume: 12
• Start Page: 632564
• End Page: 632564
• Grant/Funding Information: MD was supported in part by funds from NIH (R35CA197603), Specialized Center of Research (SCOR), and Translational Research Program (TRP) award from the Leukemia and Lymphoma Society, and the MMRF-Perelman Foundation initiative. KD was supported in part by funds from NIH (CA238471).
• Keywords: Life Sciences & Biomedicine; MGUS; Science & Technology; immune checkpoint; prevention; immune response; Immunology; myeloma and other plasma cell dyscrasias
• Research Categories: Health Sciences, Oncology

Abstract

Multiple myeloma (MM), a malignant neoplasm of plasma cells that reside in the bone marrow (BM), is universally preceded by a precursor state termed monoclonal gammopathy of undetermined significance (MGUS). Many individuals with MGUS never progress to MM or progress over many years. Therefore, MGUS provides a unique opportunity to surveil changes in the BM tumor microenvironment throughout disease progression. It is increasingly appreciated that MGUS cells carry many of the genetic changes found in MM. Prior studies have also shown that MGUS cells can be recognized by the immune system, leading to early changes in the BM immune environment compared to that of healthy individuals, including alterations in both innate and adaptive immunity. Progression to clinical MM is associated with attrition of T cells with stem memory-like features and instead accumulation of T cells with more terminally differentiated features. Recent clinical studies have suggested that early application of immune-modulatory drugs, which are known to activate both innate and adaptive immunity, can delay the progression to clinical MM. Understanding the biology of how the immune response and tumors coevolve over time is needed to develop novel immune-based approaches to achieve durable and effective prevention of clinical malignancy.