Potential Treatment for Multiple Myeloma: Immune Checkpoint Inhibitors

Jiaxin Wang,Jiaxiong Tan,Yuhong Lu

doi:10.11648/j.iji.20210903.14

Abstract

Multiple myeloma (MM) is a malignant disease in which monoclonal plasma cells proliferate abnormally. The poor prognosis of MM is always closely related to the immunosuppression of T cells. Restore the immune function of suppressed T cells may reverse the immunodeficiency in the MM microenvironment and improve prognosis. In recent years, immunosuppressive receptors such as programmed cell death receptor-1 (PD-1), T cells immunoglobulin and ITIM domain (TIGIT), Lymphocyte-Activation Gene-3 (LAG-3), T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3), Leukocyte immunoglobulin-like receptor B1 (LILRB1) and Cytotoxic T- lymphocyte antigen 4 (CTLA-4) have been discovered playing a key role in the tumor immunodeficiency microenvironment. For patients with solid tumors and some leukemia, immunotherapy targeting such receptors can significantly improve the T cells immunodeficiency. However, similar positive results were not found in MM patients, which is related to the complex immunosuppressive mechanism. At present, the understanding of immunosuppressive receptors in MM is insufficient. In this review, this paper summarized part of the studies on PD-1, TCLA-4, Tim-3, TIGIT and other popular immunosuppressive receptors in MM, in order to attract more attention, and in-depth research on the immunotherapy also to promote the immunotherapy of MM from basic research to clinical transformation as soon as possible.

Highlights

Multiple myeloma (MM) is a malignant disease caused by the abnormal proliferation of monoclonal plasma cells
Recent in-depth studies on tumor microenvironment have shown that immunosuppressive receptors such as programmed cell death receptor-1 (PD-1) [4], T cell immunoglobulin and ITIM domain (TIGIT) [5], Lymphocyte-Activation Gene 3 (LAG-3) [6], T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) [7], Leukocyte immunoglobulin-like receptor B1 (LILRB1) [8] and cytotoxic T- lymphocyte antigen 4 (CTLA-4) [9] play a key role in the formation of an immunosuppressive microenvironment
Besides studying the role of targeting PD-1/PD-L1, some researchers have found in the treatment of non-small cell lung cancer, in that the clinical response of anti-PD-1 immunotherapy does not depend on the detection of PD1/PD-L1 level, but is positively correlated with the burden of non-synonymous mutations in the patient’s somatic cells [25]

Summary

Introduction

Multiple myeloma (MM) is a malignant disease caused by the abnormal proliferation of monoclonal plasma cells. Studies have shown that the poor prognosis of MM is closely related to the immune suppression of T cells. [1] It has been reported that there are immune dysfunction mechanisms such as abnormal T cell classification ratio, low cytotoxicity and functional exhaustion in MM patients [2]. Conventional treatments can lead to premature aging phenotypes and metabolic dysfunction in T cells, which makes it even more difficult for MM patients with existing immunodeficiency to restore the immune function of. Clinical studies have shown that targeted immunosuppressive receptor immunotherapy for patients with solid tumors and some leukemias can significantly improve the T cell immunodeficiency of patients and achieve exciting clinical effects [10,11,12]. Targeting a single immunosuppressive receptor cannot well reverse T cell immune dysfunction. This article will review the research of some common immunosuppressive receptors in MM, aiming to provide more basic information and strategies for the combined anti-immunosuppressive receptor therapy of MM

Immunosuppressive Receptor

CTLA-4

Findings

Summary