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:Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity.
Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity.
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间充质干细胞(MSCs)是具有自我更新能力的多能干细胞,可调节所有参与抗肿瘤免疫的免疫细胞的表型和功能。MSCs 调节树突状细胞的抗原提呈特性,影响巨噬细胞和 CD4+ T 辅助细胞中趋化因子和细胞因子的产生,改变 CD8+ T 淋巴细胞和NK 细胞的细胞毒性,并调节髓源性抑制细胞和 T 调节细胞的产生和扩增。作为可塑性细胞,MSCs 根据邻近肿瘤浸润免疫细胞的细胞因子谱来调整其表型和功能。根据其所暴露的肿瘤微环境,MSCs 可能获得促肿瘤和抗肿瘤表型,并可能增强或抑制肿瘤生长。由于其肿瘤归巢特性,MSCs 及其外泌体可作为递送抗肿瘤药物的载体进入肿瘤细胞,减弱其活力和侵袭特性。由于许多因素影响肿瘤微环境中 MSCs 的表型和功能,更好地理解调控 MSCs、免疫细胞和肿瘤细胞之间相互作用的信号通路,将为 MSCs 在癌症免疫治疗中的临床应用铺平道路。在这篇综述文章中,我们总结了目前关于 MSCs 依赖性调节抗肿瘤免疫反应的分子和细胞机制的知识,并讨论了关于 MSCs 在恶性疾病治疗中治疗潜力的不同见解。
Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth.
Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy.
In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.
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