Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Genetic, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
J Cell Physiol. 2021 Feb;236(2):791-805. doi: 10.1002/jcp.29905. Epub 2020 Jun 27.
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of neoplastic proliferation of a plasma cell in the bone marrow that produces a monoclonal immunoglobulin. The immune checkpoint inhibitors against programmed death-1/programmed death-1 ligand and cytotoxic T-lymphocyte antigen 4 axis have demonstrated appropriate anticancer activity in several solid tumors and liquid cancers, and are rapidly transforming the practice of medical oncology. However, in a high percentage of patients, the efficacy of immune checkpoints blockade remains limited due to innate or primary resistance. Moreover, the malignancies progress in many patients due to acquired or secondary resistance, even after the clinical response to immune checkpoints' blockade. The evidence shows that multiple tumor-intrinsic and tumor-extrinsic factors and alterations in signaling pathways are involved in primary and secondary resistance to immune checkpoints blockade. Improved identification of intrinsic and extrinsic factors and mechanisms of resistance or response to immune checkpoints blockade may not only provide novel prognostic or predictive biomarkers but also guide the optimal combination/sequencing of immune checkpoint blockade therapy in the clinic. Here, we review the underlying biology and role of immune checkpoints blockade in patients with MM. Furthermore, we review the host and tumor-related factor effects on immune checkpoints blockade in MM immunotherapy.
多发性骨髓瘤（MM）是一种克隆性 B 细胞恶性肿瘤，其特征是骨髓中浆细胞的恶性增殖积累，产生单克隆免疫球蛋白。针对程序性死亡-1/程序性死亡配体 1 和细胞毒性 T 淋巴细胞抗原 4 轴的免疫检查点抑制剂已在几种实体瘤和液体癌中显示出适当的抗癌活性，并正在迅速改变肿瘤学的医学实践。然而，在很大比例的患者中，由于先天或原发性耐药，免疫检查点阻断的疗效仍然有限。此外，即使在对免疫检查点阻断有临床反应后，许多患者的恶性肿瘤仍会因获得性或继发性耐药而进展。有证据表明，多种肿瘤内在和外在因素以及信号通路的改变与免疫检查点阻断的原发性和继发性耐药有关。改善对内在和外在因素以及对免疫检查点阻断的耐药或反应机制的认识，不仅可以提供新的预后或预测生物标志物，还可以指导免疫检查点阻断治疗在临床上的最佳联合/序贯。在这里，我们回顾了免疫检查点阻断在 MM 患者中的基础生物学和作用。此外，我们还回顾了宿主和肿瘤相关因素对 MM 免疫治疗中免疫检查点阻断的影响。
