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:Targeting TIME With Phytochemicals: A Promising Approach Against Lung Cancer.
Targeting TIME With Phytochemicals: A Promising Approach Against Lung Cancer.
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肺癌在全球范围内仍是一种侵袭性强且高度流行的疾病,2022年估计导致180万人死亡,已成为癌症相关死亡的主要原因。对现有疗法的耐药性需要靶向肿瘤免疫微环境(TIME)的新方法,而TIME对疾病进展至关重要。研究表明,某些植物化学物可通过调节TIME增强抗肿瘤免疫。本系统综述旨在阐明并综合植物化学物在肺癌中发挥抗肿瘤免疫调节作用的机制,并评估其治疗潜力和转化挑战。
我们全面检索了截至2025年12月的PubMed、Web of Science和中国知网(CNKI)文献。根据植物化学物的化学结构及其在TIME中的特定靶点,对其机制进行了分析和分类。植物化学物通过多靶点策略有效重编程免疫抑制性TIME。关键作用包括抑制免疫抑制细胞——如髓源性抑制细胞(MDSCs)、Treg细胞和M2极化巨噬细胞(例如通过二氢异丹参酮I下调STAT3)——激活效应细胞(例如NK细胞、CD8+ T细胞和M1巨噬细胞),以及逆转辅助性T细胞漂移(例如panaxan和秦皮乙素)。这种多管齐下的调节通过增强CD8+ T细胞反应和克服功能性耗竭而提供更优疗效。本综述验证了植物化学物作为肺癌TIME靶向治疗的新型多靶点治疗药物的巨大潜力。未来研究应优先解决药理学挑战,以加速合理的临床整合。
Lung cancer remains an aggressive and highly prevalent disease worldwide, causing an estimated 1. 8 million deaths in 2022 and becoming a leading cause of cancer-related mortality. Resistance to current therapies necessitates novel approaches that target the tumour immune microenvironment (TIME), which is crucial for disease progression.
Studies suggest that certain phytochemicals can enhance antitumour immunity by modulating the TIME. This systematic review aimed to elucidate and synthesise the mechanisms by which phytochemicals exert antitumour immunomodulatory effects in lung cancer and to assess their therapeutic potential and translational challenges.
We comprehensively reviewed the literature from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) until December 2025. Phytochemical mechanisms were analysed and classified based on their chemical structures and specific targets within the TIME. Phytochemicals effectively reprogrammed the immunosuppressive TIME using multi-target strategies. Key actions include the inhibition of immunosuppressive cells-such as myeloid-derived suppressor cells (MDSCs), Treg cells, and M2-polarised macrophages (e. g.
, via STAT3 downregulation by dihydroisotanshinone I)-activation of effector cells (e. g. , NK cells, CD8+ T cells, and M1 macrophages), and the reversal of T helper cell drift (e. g. , panaxan and aesculetin). This multipronged modulation offers superior efficacy by enhancing CD8+ T cell responses and overcoming functional exhaustion.
This review validates the significant potential of phytochemicals as novel multi-target therapeutic agents for TIME-targeted therapy in lung cancer. Future research should prioritise addressing pharmacological challenges to accelerate rational clinical integration.
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