Therapeutics to harness the immune microenvironment in multiple myeloma  

作　　者：James J.Ignatz-Hoover James J.Driscoll 

机构地区：[1]University Hospitals,Seidman Cancer Center,Cleveland,OH 44106,USA [2]Department of Biochemistry,Case Western Reserve University,Cleveland,OH 44106,USA [3]Hematopoietic and Immune Cancer Biology Program,Case Comprehensive Cancer Center,Case Western Reserve University,Cleveland,OH 44106,USA

出　　处：《Cancer Drug Resistance》2022年第3期647-661,共15页癌症耐药（英文）

基　　金：supported by NIH R01(5R01AI139141 to JJD),University Hospitals Cleveland Medical Center/Seidman Cancer Center,and the Case Comprehensive Cancer Center.

摘　　要：Multiple myeloma(MM)remains an incurable,genetically heterogeneous disease characterized by the uncontrolled proliferation of transformed plasma cells nurtured within a permissive bone marrow(BM)microenvironment.Current therapies leverage the unique biology of MM cells and target the immune microenvironment that drives tumor growth and facilitates immune evasion.Proteasome inhibitors and immunomodulatory drugs were initially introduced to complement and have now supplanted cytotoxic chemotherapy as frontline anti-myeloma agents.Recently,monoclonal antibodies,bispecific antibodies,and chimeric antigen receptor T cells were developed to revamp the immune system to overcome immune suppression and improve patient responses.While current MM therapies have markedly extended patient survival,acquired drug resistance inevitably emerges and drives disease progression.The logical progression for the next generation of MM therapies would be to design and validate agents that prevent and/or overcome acquired resistance to immunotherapies.The complex BM microenvironment promotes resistance to both current anti-myeloma agents and emerging immunotherapies.Myeloma cells are intertwined with a complex BM immune microenvironment that contributes to the development of adaptive drug resistance.Here,we describe recently FDA-approved and investigational anti-myeloma agents that directly or indirectly target the BM microenvironment to prevent or overcome drug resistance.Synergistic effects of anti-myeloma agents may foster the development of rationally-designed drug cocktails that prevent BM-mediated resistance to immunotherapies.

关 键 词：Multiple myeloma drug resistance proteasome inhibitors IMMUNOMODULATORS IMMUNOTHERAPEUTICS adaptive resistance bone marrow microenvironment 

分 类 号：R73[医药卫生—肿瘤]