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:Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC.
Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC.
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HBV感染是肝细胞癌(HCC)发生和发展的关键风险因素,HCC是一种高度侵袭性的肿瘤,其特征是持续存在的免疫抑制微环境。本综述深入分析了HBV相关HCC,并探讨了中性粒细胞、NK 细胞和树突状细胞之间的相互作用,审视了它们在调节肿瘤相关巨噬细胞和CD8+ T细胞以及塑造肿瘤微环境中的作用。CD8+ T细胞和肿瘤相关巨噬细胞(TAMs)是HBV相关HCC免疫抑制微环境中的两个关键角色。
本研究探讨了TAMs最初被招募以对抗感染,随后如何转变,获得促肿瘤表型,转而对抗机体,促进肿瘤细胞增殖,抑制抗肿瘤免疫,并协助癌症扩散。与此同时,CD8+ T细胞对于控制HBV感染至关重要,但在持续慢性病毒炎症的刺激下变得功能失调和耗竭。本综述随后剖析了TAMs如何操纵这种免疫反应,通过精氨酸剥夺等机制进一步耗竭CD8+ T细胞功能,并创造导致耗竭的缺氧环境。
最后,本综述探讨了靶向TAMs和CD8+ T细胞的挑战和有前景的治疗途径,无论是单独靶向还是与抗病毒治疗和个性化医疗方法相结合,为改善HBV相关HCC的预后带来了希望。
HBV infection is a key risk factor for the development and progression of hepatocellular carcinoma (HCC), a highly invasive tumor, and is characterized by its persistent immunosuppressive microenvironment. This review provides an in-depth analysis of HBV-related HCC and explores the interactions between neutrophils, natural killer cells, and dendritic cells, examining their roles in regulating tumor-associated macrophages and CD8+ T cells and shaping the tumor microenvironment. Two critical players in the immunosuppressive milieu of HBV-related HCC are CD8+ T cells and tumor-associated macrophages (TAMs).
The study explores how TAMs, initially recruited to combat infection, transform, adopting a tumor-promoting phenotype, turning against the body, promoting tumor cell proliferation, suppressing anti-tumor immunity, and assisting in the spread of cancer.
Meanwhile, CD8+ T cells, crucial for controlling HBV infection, become dysfunctional and exhausted in response to persistent chronic viral inflammation. The review then dissects how TAMs manipulate this immune response, further depleting CD8+ T cell functions through mechanisms like arginine deprivation and creating hypoxic environments that lead to exhaustion.
Finally, it explores the challenges and promising therapeutic avenues that target TAMs and CD8+ T cells, either separately or in combination with antiviral therapy and personalized medicine approaches, offering hope for improved outcomes in HBV-related HCC.
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