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:Measurement of Metabolic Alteration in Immune Cells Under Hypoxia.
Measurement of Metabolic Alteration in Immune Cells Under Hypoxia.
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实体瘤中的缺氧微环境影响肿瘤细胞和浸润免疫细胞的代谢,这有助于肿瘤的强劲生长和扩张。髓源性抑制细胞(MDSCs)是TME中的异质性未成熟髓系细胞,通过颠覆T/NK细胞介导的杀伤在免疫逃逸中发挥重要作用。MDSCs的免疫抑制功能受到代谢途径的严格调控,其中缺氧起着关键作用。在本章中,我们描述了从小鼠骨髓中分离MDSCs以及在缺氧条件下测量关键代谢酶的转录组变化。该方法可应用于研究MDSCs功能,在体外模拟缺氧环境。从长远来看,该方法可用于研究特定肿瘤背景下的关键代谢改变,并有助于评估代谢靶向治疗的疗效。
The hypoxic microenvironment in solid tumors affects the metabolism of tumor cells and infiltrating immune cells, which aids in robust tumor growth and expansion. Myeloid-derived suppressor cells (MDSCs) are heterogenous immature myeloid cells in the TME, which play an essential role in immune evasion by subverting T/NK cell-mediated killing. The immunosuppressive function of MDSCs is tightly regulated to the metabolic pathways, in which hypoxia plays a critical role.
In this chapter, we describe the isolation of murine MDSCs from bone marrows and the measurement of the transcriptomic changes of essential metabolic enzymes under hypoxic conditions. This method can be applied to study MDSCs function, mimicking the hypoxic environment in vitro. This method can be utilized to investigate the critical metabolic alterations under a given tumor context and help evaluate the efficacy of metabolic-targeted therapies in the long run.
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