Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, United States.
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States.
Front Immunol. 2021 Feb 26;12:632564. doi: 10.3389/fimmu.2021.632564. eCollection 2021.
Multiple myeloma (MM), a malignant neoplasm of plasma cells that reside in the bone marrow (BM), is universally preceded by a precursor state termed monoclonal gammopathy of undetermined significance (MGUS). Many individuals with MGUS never progress to MM or progress over many years. Therefore, MGUS provides a unique opportunity to surveil changes in the BM tumor microenvironment throughout disease progression. It is increasingly appreciated that MGUS cells carry many of the genetic changes found in MM. Prior studies have also shown that MGUS cells can be recognized by the immune system, leading to early changes in the BM immune environment compared to that of healthy individuals, including alterations in both innate and adaptive immunity. Progression to clinical MM is associated with attrition of T cells with stem memory-like features and instead accumulation of T cells with more terminally differentiated features. Recent clinical studies have suggested that early application of immune-modulatory drugs, which are known to activate both innate and adaptive immunity, can delay the progression to clinical MM. Understanding the biology of how the immune response and tumors coevolve over time is needed to develop novel immune-based approaches to achieve durable and effective prevention of clinical malignancy.
多发性骨髓瘤（MM）是一种发生在骨髓（BM）中的浆细胞恶性肿瘤，普遍存在前驱状态，称为意义未明的单克隆丙种球蛋白血症（MGUS）。许多 MGUS 患者从未进展为 MM 或多年后才进展。因此，MGUS 为监测疾病进展过程中 BM 肿瘤微环境的变化提供了独特的机会。人们越来越认识到，MGUS 细胞携带了许多在 MM 中发现的遗传变化。先前的研究还表明，MGUS 细胞可以被免疫系统识别，导致 BM 免疫环境发生早期变化，与健康个体相比，包括先天和适应性免疫的改变。进展为临床 MM 与具有干细胞记忆样特征的 T 细胞耗竭有关，而具有更终末分化特征的 T 细胞则积累。最近的临床研究表明，早期应用已知可激活先天和适应性免疫的免疫调节药物可延缓临床 MM 的进展。为了开发新的基于免疫的方法来实现持久有效的预防临床恶性肿瘤，需要了解免疫反应和肿瘤如何随时间共同进化的生物学。
