肿瘤细胞治疗研究
英文原题：Targeting immune heterogeneity in liver metastases through in vivo genetic engineering.
肝脏既是核心代谢器官，也是独特的免疫耐受微环境，这使其成为肝转移（LMS）的常见部位，也是免疫治疗面临挑战的环境。
肝脏既是核心代谢器官，也是独特的免疫耐受生态位，这使其成为肝转移（LMS）的常见部位，也成为免疫治疗面临挑战的环境。人们日益认识到，肝脏驻留细胞——Kupffer细胞、Ito细胞、肝窦内皮细胞——以及浸润的髓系和淋系细胞群，共同建立了一个有利于转移定植和进展的免疫抑制微环境。对这些细胞间相互作用以及效应T细胞排斥的理解进展，凸显了新的治疗切入点。与此同时，基因递送平台的创新——从慢病毒和AAV载体到脂质纳米颗粒——以及工程化免疫细胞如CAR-T和CAR-NK细胞，正在开辟调控肝脏肿瘤生态位的途径。在此，我们综述这些对肝脏免疫生物学的认识如何为LMS的下一代免疫治疗设计提供信息，并强调将其转化为临床的机遇与挑战。
The liver is both a central metabolic organ and a uniquely tolerogenic immune niche, which makes it a frequent site of liver metastases (LMS) and a challenging environment for immunotherapy. It is increasingly appreciated that resident liver cells- Kupffer cells, Ito cells, liver sinusoidal endothelial cells - as well as infiltrating myeloid and lymphoid populations, collectively establish an immunosuppressive microenvironment that favors metastatic seeding and progression. Advances in our understanding of these cell-cell interactions and the exclusion of effector T cells, have highlighted new therapeutic entry points. In parallel, innovations in gene-delivery platforms, from lentiviral and AAV vectors to lipid nanoparticles, and in engineered immune cells such as CAR-T and CAR-NK cells, are opening avenues to modulate the hepatic tumor niche. Here we review how these insights into liver immunobiology inform the design of next-generation immunotherapies for LMS, emphasizing opportunities and challenges in translating them to the clinic.
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