RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunopharmacology of gastric cancer-deciphering immune cell subset responses and nanoparticle-mediated targeting.
Immunopharmacology of gastric cancer-deciphering immune cell subset responses and nanoparticle-mediated targeting.
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免疫细胞群体的多样性显著影响晚期胃癌的治疗效果,晚期胃癌是全球癌症死亡的主要原因之一。在单细胞分析技术的推动下,免疫药理学进展日益凸显免疫复杂性和功能异质性。传统分类包含多种亚群,包括各种T细胞(辅助性、调节性、记忆性)和B细胞(浆细胞、记忆性、调节性)。固有免疫细胞如巨噬细胞、NK 细胞和树突状细胞也存在多种功能状态。这些亚群表现出不同的药理反应特征,而这些特征往往被批量分析所掩盖。本综述探讨胃癌肿瘤微环境中关键免疫细胞亚群对当前治疗模式的差异性反应,涵盖细胞毒性化疗、分子靶向药物以及免疫治疗如检查点抑制剂。
我们深入探讨亚群特异性药物效应的分子过程、与特定免疫细胞状态相关的潜在治疗耐药机制,以及肿瘤微环境对免疫亚群药理学的影响。
此外,我们讨论基于纳米颗粒的药物递送系统的应用和潜力,这些系统专门设计用于靶向不同的免疫细胞亚群,旨在增强免疫调节疗效、有利地重塑亚群组成、克服耐药性并最小化毒性,以实现对晚期胃癌更精准有效的治疗。
The diverse landscape of immune cell populations significantly influences therapeutic outcomes in advanced gastric cancer, a leading cause of cancer mortality worldwide. Progress in immunopharmacology, aided by single-cell analytics, increasingly highlights immune complexity and functional heterogeneity. Conventional categories contain diverse subsets, including various T cells (helper, regulatory, memory) and B cells (plasma, memory, regulatory).
Innate immune cells like macrophages, natural killer cells, and dendritic cells also exist in various functional states. These subsets exhibit distinct pharmacological response profiles that are often obscured by bulk analyses. This review explores the differential responses of critical immune cell subsets within the gastric cancer tumor microenvironment to current therapeutic modalities, encompassing cytotoxic chemotherapy, molecular targeted agents, and immunotherapies such as checkpoint inhibitors.
We delve into the molecular processes underlying subset-specific drug effects, potential mechanisms of therapeutic resistance linked to specific immune cell states, and the influence of the tumor microenvironment on immune subset pharmacology.
Furthermore, we discuss the application and potential of nanoparticle-based drug delivery systems specifically engineered to target distinct immune cell subpopulations, aiming to enhance immunomodulatory efficacy, reshape subset repertoires favorably, overcome resistance, and minimize toxicity for more precise and effective treatment of advanced gastric cancer.
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