Curated Papers > Recent high-impact research on the "tumor microenvironment" (IF ≥ 30, past 5 years)

Kir2.1 channel: Macrophage plasticity in tumor microenvironment.

Literature Information

DOI	10.1016/j.cmet.2022.10.009
PMID	36323230
Journal	Cell metabolism
Impact Factor	30.9
JCR Quartile	Q1
Publication Year	2022
Times Cited	3
Keywords	Kir2.1 channel, tumor microenvironment, macrophage plasticity, metabolic reprogramming, tumor-associated macrophages
Literature Type	Journal Article, Comment
ISSN	1550-4131
Pages	1613-1615
Issue	34(11)
Authors	Umar Al-Sheikh, Lijun Kang

TL;DR

Chen et al. demonstrate that elevated intratumoral potassium ions limit the plasticity of tumor-associated macrophages (TAMs) in the tumor microenvironment, revealing a crucial link between ion channel dysregulation and immune response. Their findings indicate that inhibiting the Kir2.1 potassium channel can effectively reprogram pro-tumor M2-TAMs into tumoricidal M1-like states, suggesting a potential therapeutic strategy to enhance anti-tumor immunity.

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Kir2.1 channel · tumor microenvironment · macrophage plasticity · metabolic reprogramming · tumor-associated macrophages

Abstract

Diverse ion channels have dysregulated functional expression in the tumor microenvironment (TME). In this issue of Cell Metabolism, Chen et al. reveal that high intratumoral K+ ions restrict the plasticity of tumor-associated macrophages (TAMs). Inhibition of the Kir2.1 potassium channel induced metabolic reprogramming and repolarization of pro-tumor M2-TAMs to tumoricidal M1-like states.

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Primary Questions Addressed

1. How does the dysregulation of other ion channels in the tumor microenvironment affect macrophage function and plasticity?
2. What specific metabolic pathways are involved in the repolarization of M2-TAMs to M1-like states when Kir2.1 is inhibited?
3. Are there potential therapeutic implications for targeting Kir2.1 in the treatment of tumors with high levels of M2-TAMs?
4. How do different tumor types influence the expression and role of Kir2.1 in macrophage plasticity?
5. What are the implications of Kir2.1 channel modulation on the overall immune response within the tumor microenvironment?

Key Findings

Key Insights:

1. Research Background and Objective: The tumor microenvironment (TME) is characterized by various alterations, including the dysregulation of ion channels that can affect the functional expression of immune cells. Specifically, this study investigates the role of the Kir2.1 potassium channel in regulating the plasticity of tumor-associated macrophages (TAMs) within the TME. The objective is to understand how high levels of intratumoral potassium ions influence TAM behavior and to explore potential therapeutic strategies for reprogramming these cells.

2. Main Methods and Findings: The researchers conducted experiments to examine the effects of high K+ concentrations in the TME on the functional state of TAMs. They utilized both in vitro and in vivo models to assess the expression of Kir2.1 channels and the resultant metabolic changes in macrophages. The findings revealed that the inhibition of the Kir2.1 channel led to significant metabolic reprogramming of the TAMs, facilitating a shift from a pro-tumor M2 phenotype towards a tumoricidal M1-like state. This repolarization is critical as it indicates that targeting the Kir2.1 channel can effectively alter the immune landscape within tumors.

3. Core Conclusion: The study concludes that high levels of potassium ions in the TME restrict the plasticity of TAMs by maintaining their pro-tumor M2 phenotype through the Kir2.1 potassium channel. Inhibiting Kir2.1 not only disrupts this stabilizing effect but also promotes a functional switch toward an M1-like macrophage state, thereby enhancing the anti-tumor immune response. This finding underscores the potential of ion channel modulation as a therapeutic strategy in cancer treatment.

4. Research Significance and Impact: This research provides critical insights into the complex interactions between ion channels and immune cell behavior in the TME. The identification of Kir2.1 as a key regulator of TAM plasticity offers a novel target for therapeutic intervention aimed at reprogramming the immune response against tumors. By leveraging the understanding of ion channel dynamics, this study opens avenues for developing new treatments that could improve the efficacy of existing cancer therapies. Moreover, it highlights the importance of the TME in shaping immune cell functionality, which may influence future research directions in cancer immunology and therapy. Overall, the findings contribute to a deeper understanding of macrophage biology and its implications for enhancing anti-tumor immunity.

Literatures Citing This Work

1. Characterisation of GFAP-Expressing Glial Cells in the Dorsal Root Ganglion after Spared Nerve Injury. - Elena A Konnova;Alexandru-Florian Deftu;Paul Chu Sin Chung;Marie Pertin;Guylène Kirschmann;Isabelle Decosterd;Marc R Suter - International journal of molecular sciences (2023)
2. Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities. - Yujing Qian;Yujia Yin;Xiaocui Zheng;Zhaoyuan Liu;Xipeng Wang - Biomarker research (2024)
3. Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets. - Guohao Wei;Bin Li;Mengyang Huang;Mengyao Lv;Zihui Liang;Chuandong Zhu;Lilin Ge;Jing Chen - MedComm (2025)

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