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:Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review).
Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review).
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缺氧肿瘤微环境(TME)在实体瘤的发展中普遍存在,其激活癌细胞中的缺氧诱导因子(HIFs)及其下游信号通路,从而促进肿瘤进展和免疫逃逸。
然而,在构成固有免疫和适应性免疫系统的各种免疫细胞中,HIFs具有更为复杂的功能;此外,HIFs的不同亚型在时空条件下发挥不同的功能。HIFs有利于各种免疫细胞适应缺氧TME。HIF-α的稳定性可以调节代谢并直接调节免疫基因的表达。
此外,HIF信号的激活在某些肿瘤环境中也可能抑制免疫细胞的发育,影响抗原识别和杀伤过程,从而协助癌细胞免疫逃逸。因此,更全面地理解HIF信号与免疫细胞之间的关系可能为多种类型癌症的免疫治疗带来实质性益处。
本研究综述了HIFs在免疫中的作用,包括其在T细胞、B细胞、巨噬细胞、中性粒细胞、树突状细胞和NK 细胞中的作用。还讨论了HIF靶向治疗在临床应用中的有效性、相关挑战以及精准靶向药物递送系统的开发。本综述可能有助于研究人员理解缺氧微环境中的肿瘤免疫过程。旨在为癌症免疫治疗和延长患者总生存期提供新策略。
<p>Hypoxic tumor microenvironment (TME) is a common occurrence in the development of solid tumors, which activates hypoxia‑inducible factors (HIFs) and their downstream signaling pathways in cancer cells to facilitate tumor progression and immune escape.
However, among the various immune cells that constitute innate and adaptive immune systems, HIFs have a more intricate function; moreover, different isoforms of HIFs play different functions under spatial and temporal conditions. HIFs are conducive to the adaptation of various immune cells to the hypoxic TME. The stability of HIF‑α can regulate metabolism and directly regulate the expression of immune genes.
Additionally, the activation of HIF signaling may also inhibit the development of immune cells in some tumor environments, affecting the antigen recognition and killing processes to assist cancer cells in immune escape.
Therefore, understanding the relationship between HIF signaling and immune cells more comprehensively may yield substantial benefits for the immunotherapy of various types of cancer. The present study reviewed the role of HIFs in immunity, including their role in T cells, B cells, macrophages, neutrophils, dendritic cells and natural killer cells.
It also discussed the effectiveness of HIF targeted therapy in clinical application, the challenges associated with it and the development of a precise targeting drug delivery system. The present review may help researchers comprehend the tumor immune process in a hypoxic microenvironment. It aimed to offer novel strategies for cancer immunotherapy and prolonging the overall survival of patients. </p>.
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