CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：New horizons in our understanding of precursor multiple myeloma and early interception.
New horizons in our understanding of precursor multiple myeloma and early interception.
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多发性骨髓瘤是一种无法治愈的浆细胞恶性肿瘤，经过数十年克隆性浆细胞的选择和恶性转化逐步演进。从前驱状态发展为症状性疾病的过程中，浆细胞内基因组改变日趋复杂，微环境也重塑为免疫抑制状态。值得注意的是，在晚期患者中，肿瘤逃逸和免疫功能障碍的类似机制会导致其对现代 T 细胞疗法耐药，例如 T 细胞衔接双特异性抗体和嵌合抗原受体（CAR）T 细胞。因此，越来越多临床试验正在评估这些疗法用于新诊断多发性骨髓瘤和高危冒烟型多发性骨髓瘤患者的疗效与安全性。本综述总结前驱状态进展为症状性骨髓瘤过程中肿瘤内在和外在机制的当前认识，并讨论早期干预的依据，包括采用 T 细胞重定向疗法。
Multiple myeloma is an incurable plasma cell malignancy that evolves over decades through the selection and malignant transformation of monoclonal plasma cells. The evolution from precursor states to symptomatic disease is characterized by an increasing complexity of genomic alterations within the plasma cells and a remodelling of the microenvironment towards an immunosuppressive state.
Notably, in patients with advanced disease, similar mechanisms of tumour escape and immune dysfunction mediate resistance to modern T cell-based therapies, such as T cell-engaging bispecific antibodies and chimeric antigen receptor (CAR)-T cells.
Thus, an increasing number of clinical trials are assessing the efficiency and safety of these therapies in individuals with newly diagnosed multiple myeloma and high-risk smoldering multiple myeloma. In this Review, we summarize the current knowledge about tumour intrinsic and extrinsic processes underlying progression from precursor states to symptomatic myeloma and discuss the rationale for early interception including the use of T cell-redirecting therapies.
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