为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
肿瘤细胞治疗研究
英文原题:Tumor-associated macrophages: The key player in hepatoblastoma microenvironment and the promising therapeutic target.
Tumor-associated macrophages: The key player in hepatoblastoma microenvironment and the promising therapeutic target.
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肝母细胞瘤(HB)是最常见的儿童肝脏肿瘤,其肿瘤微环境主要呈现髓系免疫格局,其中肿瘤相关巨噬细胞(TAMs)被认为是核心组成部分。TAMs与HB细胞之间的交互作用显著影响肿瘤行为。TAM来源的因子参与肿瘤增殖和血管侵犯。另一方面,HB细胞分泌组吸引、刺激并重编程TAMs,使其变为免疫抑制状态以利于肿瘤侵袭,而非其对抗肿瘤生长的先天作用,这种交互作用有时形成双向反馈环路,使肿瘤更具毒力和对常规治疗更具抵抗力。因此,TAMs是大多数已提出的HB免疫治疗策略的共同要素。巨噬细胞免疫检查点抑制剂、巨噬细胞介导的抗体依赖性细胞吞噬作用以及新型嵌合抗原受体巨噬细胞疗法(CAR Mφ)目前正在试验中。在本综述中,我们将总结TAMs的重要性及其作为HB治疗靶点的潜在作用。
The tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor-associated macrophages (TAMs) are considered the core component. The crosstalk between TAMs and HB cells markedly influences tumor behavior. TAM-derived factors are involved in tumor proliferation and vascular invasion. On the other hand, HB cell secretome attracts, stimulates, and reprograms TAMs to be immunosuppressive in favor of tumor invasion, rather than their innate role in combating tumor growth, such crosstalk sometimes forms bidirectional feedback loops, making the tumor more virulent and resistant to routine therapeutics.
Consequently, TAMs are the common denominator of most suggested HB immunotherapeutic strategies. Macrophage immune checkpoint inhibitors, macrophage-mediated antibody-dependent cellular phagocytosis, and the novel chimeric antigen receptor macrophage therapy (CAR Mφ) are currently under trial. In this review, we will summarize the significance of TAMs and their potential role as a therapeutic target in HB.
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