决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,表现出显著的功能可塑性,根据所处的微环境信号,既可充当促进肿瘤进展的免疫抑制细胞,也可充当支持抗肿瘤免疫的免疫刺激细胞。这些细胞促进血管生成、转移、免疫抑制和治疗耐药。然而,当被适当地重编程后,TAMs可以直接杀死或吞噬癌细胞,和/或激活抗肿瘤T细胞和NK 细胞反应。在本文中,我们综述了当前靶向TAMs的治疗策略,包括针对巨噬细胞相关受体、信号通路以及表观遗传和代谢调节因子的方法。我们还讨论了新兴的TAM靶向治疗模式,包括基于细胞因子的疗法、细胞疗法、双特异性抗体、巨噬细胞靶向纳米平台以及抗TAMCAR-T 细胞方法,重点阐述了它们增强抗肿瘤免疫和改善临床结局的潜力。
Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment and exhibit remarkable functional plasticity, acting as either immunosuppressive cells that promote tumor progression or immunostimulatory cells that can support antitumor immunity, depending on the prevailing microenvironmental cues. These cells promote angiogenesis, metastasis, immune suppression, and therapy resistance. However, when appropriately reprogrammed, TAMs can directly kill or phagocytose cancer cells and/or activate antitumor T cell and natural killer cell responses. In this article, we review current therapeutic strategies targeting TAMs, including approaches directed against macrophage-associated receptors, signaling pathways, and epigenetic and metabolic regulators. We also discuss emerging TAM-targeted therapeutic modalities, including cytokine-based therapies, cell-based therapies, bispecific antibodies, macrophage-targeted nanoplatforms, and anti-TAM chimeric antigen receptor T-cell approaches, highlighting their potential to enhance antitumor immunity and improve clinical outcomes.
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