Leblay Noémie, Maity Ranjan, Hasan Fajer, Neri Paola
Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.
Front Oncol. 2020 May 5;10:636. doi: 10.3389/fonc.2020.00636. eCollection 2020.
Immunotherapy has recently emerged as a promising treatment option for multiple myeloma (MM) patients. Profound immune dysfunction and evasion of immune surveillance are known to characterize MM evolution and disease progression. Along with genomic changes observed in malignant plasma cells, the bone marrow (BM) milieu creates a protective environment sustained by the complex interaction of BM stromal cells (BMSCs) and malignant cells that using bidirectional connections and cytokines released stimulate disease progression, drug resistance and enable immune escape. Local immune suppression and T-cell exhaustion are important mediating factors of clinical outcomes and responses to immune-based approaches. Thus, further characterization of the defects present in the immune system of MM patients is essential to develop novel therapies and to repurpose the existing ones. This review seeks to provide insights into the mechanisms that promote tumor escape, cause inadequate T-cell stimulation and impaired cytotoxicity in MM. Furthermore, it highlights current immunotherapies being used to restore adaptive T-cell immune responses in MM and describes strategies created to escape these multiple immune evasion mechanisms.
免疫疗法最近已成为多发性骨髓瘤（MM）患者一种有前景的治疗选择。已知严重的免疫功能障碍和免疫监视逃避是MM演变和疾病进展的特征。除了在恶性浆细胞中观察到的基因组变化外，骨髓（BM）微环境通过BM基质细胞（BMSC）与恶性细胞的复杂相互作用创造了一个保护环境，这种相互作用利用双向连接和释放的细胞因子刺激疾病进展、耐药性并实现免疫逃逸。局部免疫抑制和T细胞耗竭是临床结果和对基于免疫的方法反应的重要介导因素。因此，进一步表征MM患者免疫系统中存在的缺陷对于开发新疗法和重新利用现有疗法至关重要。本综述旨在深入了解促进MM肿瘤逃逸、导致T细胞刺激不足和细胞毒性受损的机制。此外，它强调了目前用于恢复MM中适应性T细胞免疫反应的免疫疗法，并描述了为逃避这些多种免疫逃逸机制而创建的策略。
