Dissecting molecular mechanisms of immune microenvironment dysfunction in multiple myeloma and precursor conditions  

作　　者：Maria Moscvin Benjamin Evans Giada Bianchi 

机构地区：[1]Department of Medicine,Division of Hematology,Brigham and Womens Hospital,Boston,MA 02115,USA [2]Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,Boston,MA 02115,USA [3]Department of Medicine,Stanford University,Stanford,CA 94305,USA

出　　处：《Journal of Cancer Metastasis and Treatment》2023年第1期221-245,共25页癌症转移与治疗（英文版）

基　　金：This work was supported in part by NIH/NCI K08CA245100 grant(Giada Bianchi);by the American Italian Cancer Foundation Research Fellowship(Maria Moscvin);the Donald C.Brockman Memorial Research Grant from the Amyloidosis Foundation(Maria Moscvin).

摘　　要：Multiple myeloma(MM)is a disease of clonally differentiated plasma cells.MM is almost always preceded by precursor conditions,monoclonal gammopathy of unknown significance(MGUS),and smoldering MM(SMM)through largely unknown molecular events.Genetic alterations of the malignant plasma cells play a critical role in patient clinical outcomes.Del(17p),t(4;14),and additional chromosomal alterations such as del(1p32),gain(1q)and MYC translocations are involved in active MM evolution.Interestingly,these genetic alterations appear strikingly similar in transformed plasma cell(PC)clones from MGUS,SMM,and MM stages.Recent studies show that effectors of the innate and adaptive immune response show marked dysfunction and skewing towards a tolerant environment that favors disease progression.The MM myeloid compartment is characterized by myeloid-derived suppressor cells(MDSCs),dendritic cells as well as M2-like phenotype macrophages that promote immune evasion.Major deregulations are found in the lymphoid compartment as well,with skewing towards immune tolerant Th17 and Treg and inhibition of CD8+cytotoxic and CD4+activated effector T cells.In summary,this review will provide an overview of the complex cross-talk between MM plasma cells and immune cells in the microenvironment and the molecular mechanisms promoting progression from precursor states to full-blown myeloma.

关 键 词：Multiple myeloma plasma cells immune-microenvironment immune response IMMUNOTHERAPY 

分 类 号：R733.3[医药卫生—肿瘤]