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.
肿瘤细胞治疗研究
英文原题:Immune cell engagers in lung cancer.
Immune cell engagers in lung cancer.
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近年来,随着肿瘤微环境的不断揭示和免疫治疗的持续进展,肺癌治疗范式取得了显著进展。作为一种新兴的免疫治疗模式,免疫细胞衔接器(ICEs)旨在通过靶向肿瘤并激活T细胞、NK细胞和髓系细胞等免疫效应细胞,有效调动机体的抗肿瘤免疫应答。近期研究表明,以双特异性T细胞衔接器(BiTEs)为代表的T细胞衔接器(TCEs)能够增强肺癌微环境中T细胞的免疫活性,并在体外和体内实验中展现出显著的抗肿瘤效应。然而,肺癌微环境的高度异质性及其复杂的免疫抑制网络限制了ICEs的治疗疗效。同时,在提高靶细胞特异性、降低对非靶细胞的毒性以及优化药代动力学等方面仍存在关键挑战。本综述系统总结了ICEs在肺癌免疫治疗中的作用机制及最新进展,探讨了下一代ICEs的创新发展方向,并强调了其在推动肺癌免疫治疗范式转变方面的巨大潜力。
In recent years, significant progress has been made in lung cancer treatment paradigms with the continuous unraveling of the tumor microenvironment and the ongoing advancement of immunotherapy. As an emerging immunotherapy modality, Immune Cell Engagers (ICEs) aim to effectively mobilize the body's antitumor immune response by targeting tumors and activating immune effector cells such as T cells, NK cells, and myeloid cells.
Recent studies have indicated that T-cell engagers (TCEs), exemplified by bispecific T-cell engagers (BiTEs), can enhance T-cell immunological activity within the lung cancer microenvironment and demonstrate significant antitumor effects in both in vitro and in vivo experiments.
However, the highly heterogeneous nature of the lung cancer microenvironment and its complex immunosuppressive networks limit the therapeutic efficacy of ICEs. Meanwhile, key challenges remain in improving target cell specificity, lowering toxicity to non-target cells, and optimizing pharmacokinetics.
This review systematically summarizes the mechanisms of action and recent advances of ICEs in lung cancer immunotherapy, explores innovative development directions for next-generation ICEs, and highlights their significant potential in driving paradigm shifts in lung cancer immunotherapy.
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