多发性骨髓瘤微环境介导的免疫逃逸机制研究

Research on the mechanism of immune escape mediated by microenvironment in multiple myeloma

多发性骨髓瘤(MM)是一种由骨髓浆细胞异常增生引起的血液系统恶性肿瘤。疾病的进展受到免疫抑制肿瘤微环境(TME)的强烈调控,这种微环境的变化有利于肿瘤细胞的扩散。随着新型药物的临床应用,患者的生存状况已得到很大改善,如今,几种基于T细胞的免疫疗法,如双特异性抗体、免疫检查点抑制剂和嵌合抗原受体T细胞免疫疗法(CAR-T),正在成功进入免疫治疗领域,在临床试验中取得了非常有望的结果。然而,与临床化疗中观察到的情况相似,MM细胞似乎能够逃避免疫疗法,特别是通过与骨髓微环境的相互作用。本文总结了疾病进展过程中骨髓微环境细胞成分的变化以及所涉及的相关信号通路,旨在阐述骨髓微环境介导MM细胞免疫逃逸的潜在作用机制。

Multiple myeloma(MM)is a malignant tumor of the hematological system caused by abnormal proliferation of plasma cells in bone marrow.The progression of the disease is strongly regulated by immunosuppressive tumor microenvironment(TME),which is beneficial to the spread of tumor cells.The survival of patients have been greatly improved with the clinical application of new drugs.At present,several T cell-based immunotherapies,such as bispecific antibodies,immune checkpoint inhibitors and chimeric antigen receptor T-cell immunotherapy(CAR-T),are successfully entering the field of immunotherapy with very promising results in clinical trials.However,similar to what has been observed in clinical chemotherapy,MM cells appear to be able to evade immunotherapy,especially through interaction with the bone marrow microenvironment.This paper summarizes the changes in cellular composition and related signaling pathways in bone marrow microenvironment during the disease progression,in order to explain the potential mechanism of immune escape of MM cells mediated by the bone marrow microenvironment.