基于调节性B淋巴细胞的肿瘤免疫微环境在多发性骨髓瘤发病和免疫治疗中的作用及机制研究

The introduction of highly effective anti-myeloma new agents ushered in the era of targeted therapies which brought about significant improvements in patient overall survival (OS). Today, the observation that selected Multiple Myeloma (MM) cases can benefit from immunotherapy with hematopoietic stem cell transplant (HSCT) suggests that the future of MM therapy may be in immunotherapy combinations. While it is well-known that MM arises from terminally differentiated B cells, the specific role of various B cell subsets in MM pathogenesis remains unclear. Regulatory B cells (Bregs) are recently discovered as a subset of B cells that possess immunosuppressive functions and we have demonstrated, for the first time, that they contribute to the immunosuppressive bone marrow microenvironment in MM. However, the exact mechanisms by which Bregs exert their suppressive function remains to be elucidated. Moving forward, we therefore aim to study: ① the origin, differentiation and in vitro induction of Bregs in MM, ② based on the resource advantages of the research unit as a biological immunotherapy platform for MM patients, correlation between Bregs and immunotherapeutic efficacy of MM patients (mainly enrolling MM cases obtaining interferon-α maintanence after autologous hematopoietic stem cell transplantation) will be explored. This study is expected to provide new ideas for MM targeted immunotherapy.

多发性骨髓瘤(MM)以其诊治在新药时代的迅猛发展而倍受关注；作为肿瘤免疫治疗时代的引领者，MM再度成为目前的学术热点。尽管MM是发生于B细胞终末分化阶段的淋巴瘤，B细胞亚群在MM发病中的具体作用并不明朗。调节性B细胞(Bregs)是新近发现的一类具有免疫抑制功能的B细胞亚群；在完成NSFC青年基金课题中，我们率先证实，Bregs参与了MM骨髓免疫微环境的建立。但Bregs在MM免疫微环境中如何发挥作用尚不得知。因此，我们拟从如下层面：①Bregs在MM中的起源、分化与体外诱导，②基于研究单位作为MM患者生物免疫治疗平台的资源优势，探讨Bregs与MM患者免疫治疗（自体移植后干扰素α维持MM患者为主要研究对象，CART等为次要对象）疗效的相关性。本研究有望为MM免疫靶向治疗提供新思路。