Abstract
Multiple myeloma (MM) is usually diagnosed in older adults at the time of immunosenescence, a collection of age-related changes in the immune system that contribute to increased susceptibility to infection and cancer. The MM tumor microenvironment and cumulative chemotherapies also add to defects in immunity over the course of disease. In this review we discuss how mouse models have furthered our understanding of the immune defects caused by MM and enabled immunotherapeutics to progress to clinical trials, but also question the validity of using immunodeficient models for these purposes. Immunocompetent models, in particular the 5T series and Vk⁎MYC models, are increasingly being utilized in preclinical studies and are adding to our knowledge of not only the adaptive immune system but also how the innate system might be enhanced in anti-MM activity. Finally we discuss the concept of immune profiling to target patients who might benefit the most from immunotherapeutics, and the use of humanized mice and 3D culture systems for personalized medicine.
Highlights
Multiple myeloma (MM) is a malignancy of plasma cells that reside within a supportive niche in the bone marrow (BM) [1, 2]
Monoclonal gammopathy of undetermined significance (MGUS) is a preceding, benign phase to MM, where a monoclonal paraprotein is detected in the peripheral blood but plasma cells account for less than 10% of BM haematological cells [3, 4]
This review aims to encompass how mouse models can contribute to our understanding of the MM immune microenvironment and of the clinical use of immunotherapeutics and other novel agents in human MM
Summary
Multiple myeloma (MM) is a malignancy of plasma cells that reside within a supportive niche in the bone marrow (BM) [1, 2]. Smoldering myeloma (SMM) is asymptomatic, but plasma cells account for at least 10% of BM haematological cells. Acquired immune paresis complicates advanced disease due to residual hypogammaglobulinemia, B cell hypoplasia [5], the effects of cumulative chemotherapies [6,7,8], and an ageing T cell population [9, 10]. As our knowledge of immunosenescence and T cell exhaustion within the chronic inflammatory environment of MM advances, evaluating the effectiveness of immunotherapeutics within a tumor microenvironment in an aged host is paramount.
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