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:Polysaccharides: Natural candidates for targeting immunometabolic regulation in hepatocellular carcinoma (Review).
Polysaccharides: Natural candidates for targeting immunometabolic regulation in hepatocellular carcinoma (Review).
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
肝细胞癌(HCC)是全球癌症相关发病率和死亡率的主要原因之一。HCC的发病机制主要与慢性肝病相关,由持续性肝损伤、慢性炎症和异常肝细胞再生的恶性循环所驱动。在这一复杂的病理背景下,肿瘤免疫微环境(TIME)重塑、代谢失调和肠-肝轴失衡共同促进HCC的发生和进展。鉴于传统治疗方式对如此多层面的病理疗效有限,迫切需要探索安全、有效且能够多靶点调控的新策略。天然多糖作为一类生物活性大分子,已成为有前景的防治候选物。多糖不仅通过调节细胞周期进程、诱导凋亡以及抑制侵袭和转移来直接抑制HCC细胞的恶性表型,还能发挥强效的免疫调节作用。
具体而言,它们激活关键免疫效应细胞,包括细胞毒性T淋巴细胞、树突状细胞、NK 细胞和肿瘤相关巨噬细胞,从而逆转免疫抑制并重塑TIME。
此外,多糖能够调节肠道菌群及其代谢产物,富集有益菌群,并增强肠道屏障完整性。这些作用随后影响肝内免疫反应和炎症状态,通过“肠-肝-免疫”轴实现系统性干预。本综述系统概述了多糖对抗HCC的多方面机制,包括直接抗肿瘤作用、调节TIME以及调控肠道菌群。通过综合现有证据,本综述旨在提供关键视角,以推进对多糖治疗HCC机制的理解并促进其临床转化。
Hepatocellular carcinoma (HCC) is a leading cause of cancer‑related morbidity and mortality worldwide. HCC pathogenesis is predominantly associated with chronic liver disease, driven by a vicious cycle of persistent hepatic injury, chronic inflammation and aberrant hepatocyte regeneration. Within this complex pathological landscape, remodeling of the tumor immune microenvironment (TIME), metabolic dysregulation and gut‑liver axis imbalance collectively contribute to HCC initiation and progression. Given the limited efficacy of conventional therapeutic modalities against such multifaceted pathologies, there is an urgent need to explore novel strategies that are safe, effective and capable of multi‑target regulation.
Natural polysaccharides, a class of bioactive macromolecules, have emerged as promising candidates for prevention and treatment. Polysaccharides not only directly suppress malignant phenotypes in HCC cells by modulating cell cycle progression, inducing apoptosis, and inhibiting invasion and metastasis, but also exert potent immunomodulatory effects.
Specifically, they activate key immune effectors, including cytotoxic T lymphocytes, dendritic cells, natural killer cells and tumor‑associated macrophages, thereby reversing immunosuppression and reshaping the TIME.
Furthermore, polysaccharides can modulate the gut microbiota and its metabolites, enrich beneficial bacterial taxa, and reinforce intestinal barrier integrity. These actions subsequently influence intrahepatic immune responses and inflammatory status, achieving systemic intervention via the 'gut‑liver‑immune' axis.
The present review provides a systematic overview of the multifaceted mechanisms by which polysaccharides combat HCC, including direct antitumor effects, modulation of the TIME and regulation of the gut microbiota. By synthesizing current evidence, the present review aims to offer critical perspectives to advance the mechanistic understanding and facilitate the clinical translation of polysaccharides for HCC treatment.
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