小柯机器人

浙江大学医学院Di Wang和Kefeng Ding共同合作近期取得重要工作进展。他们的最新研究揭示了肿瘤相关的巨噬细胞通过Kir2.1被肿瘤内高钾所塑造。这一研究成果2022年9月13日在线发表于《细胞—代谢》杂志上。

研究人员揭示了肿瘤内高K⁺抑制了肿瘤相关巨噬细胞（TAM）的抗肿瘤能力。他们将内向整流的K⁺通道Kir2.1确定为高K⁺ TME中TAM功能极化的中央调节剂，它的条件性消耗使TAM重新极化为抗肿瘤状态，从而提高了局部抗肿瘤免疫力。Kir2.1缺乏会干扰电化学依赖的谷氨酰胺摄取，导致TAM代谢重编程从氧化磷酸化走向糖酵解。Kir2.1阻断减弱小鼠肿瘤和患者来源的异种移植物生长。总的来说，他们的研究结果表明，Kir2.1是在离子失衡TME中恢复TAM抗肿瘤能力的决定因素和潜在治疗靶点。

据介绍，肿瘤微环境（TME）是一个独特的生态位，由所有肿瘤内细胞间的持续相互作用所控制。特别是，肿瘤内高钾（K⁺）对T细胞显示出免疫抑制能力。然而，作为一种与局部坏死相关的广泛癌症特征，这种离子干扰对先天免疫的影响尚不清楚。

附：英文原文

Title: Tumor-associated macrophages are shaped by intratumoral high potassium via Kir2.1

Author: Sheng Chen, Wenyu Cui, Zhexu Chi, Qian Xiao, Tianyi Hu, Qizhen Ye, Kaixiang Zhu, Weiwei Yu, Zhen Wang, Chengxuan Yu, Xiang Pan, Siqi Dai, Qi Yang, Jiacheng Jin, Jian Zhang, Mobai Li, Dehang Yang, Qianzhou Yu, Quanquan Wang, Xiafei Yu, Wei Yang, Xue Zhang, Junbin Qian, Kefeng Ding, Di Wang

Issue&Volume: 2022-09-13

Abstract: The tumor microenvironment (TME) is a unique niche governed by constant crosstalkwithin and across all intratumoral cellular compartments. In particular, intratumoralhigh potassium (K+) has shown immune-suppressive potency on T cells. However, as a pan-cancer characteristicassociated with local necrosis, the impact of this ionic disturbance on innate immunityis unknown. Here, we reveal that intratumoral high K+ suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). We identifythe inwardly rectifying K+ channel Kir2.1 as a central modulator of TAM functional polarization in high K+ TME, and its conditional depletion repolarizes TAMs toward an anti-tumor state, sequentiallyboosting local anti-tumor immunity. Kir2.1 deficiency disturbs the electrochemicallydependent glutamine uptake, engendering TAM metabolic reprogramming from oxidativephosphorylation toward glycolysis. Kir2.1 blockade attenuates both murine tumor- andpatient-derived xenograft growth. Collectively, our findings reveal Kir2.1 as a determinantand potential therapeutic target for regaining the anti-tumor capacity of TAMs withinionic-imbalanced TME.

DOI: 10.1016/j.cmet.2022.08.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00359-X

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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