Immune network remodeling driven by ferroptosis: Bidirectional interaction mechanisms among multiple immune cells in the lung cancer immune microenvironment (Review)

Qu,Fei; Tong,Jiale; Qian,Weiwei; He,Qian

doi:10.3892/or.2026.9140

July-2026 Volume 56 Issue 1

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July-2026 Volume 56 Issue 1

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Review Open Access

Immune network remodeling driven by ferroptosis: Bidirectional interaction mechanisms among multiple immune cells in the lung cancer immune microenvironment (Review)

Authors:
- Fei Qu
- Jiale Tong
- Weiwei Qian
- Qian He
View Affiliations / Copyright

Affiliations: Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Institute of Disaster Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China

Copyright: © Qu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 135
|
Published online on: May 26, 2026

https://doi.org/10.3892/or.2026.9140
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Abstract

The efficacy of immunotherapy for lung cancer is largely constrained by the highly complex and dynamically evolving tumor immune microenvironment (TIME). Previous studies have mainly focused on single immune checkpoints or individual immune cell types, thus hindering the comprehensive elucidation of variations in immune responses and the emergence of resistance. Ferroptosis, a form of programmed cell death characterized by iron‑dependent lipid peroxidation imbalance, has emerged as a pivotal hub linking tumor metabolism, cellular fate and immune regulation due to high dependence on metabolic states and its capacity to release multiple immunomodulatory signals. The unique environment of lung tissue, characterized by high oxygen levels, active lipid metabolism and easily disrupted iron homeostasis, provides a distinct biological foundation for the initiation and amplification of ferroptosis within the lung cancer TIME. Increasing evidence indicates that ferroptosis affects not only tumor cell survival, but also immune regulation. Through lipid peroxidation products, iron‑related metabolites and damage‑associated molecular patterns, it forms bidirectional regulatory networks with multiple immune cell subsets, including CD8⁺ T‑cells, dendritic cells, macrophages, natural killer cells and neutrophils, thereby shaping the functional state of the immune microenvironment. Distinct from previous reviews that broadly discuss ferroptosis in cancer immunity or the tumor microenvironment, the present review specifically focuses on the lung cancer‑specific immune microenvironment and integrates ferroptosis‑mediated bidirectional interactions across multiple immune cell subsets. The present review emphasizes that ferroptosis should not be viewed merely as a tumoricidal form of cell death, but as a context‑dependent immunometabolic hub that drives immune network remodeling in lung cancer. By this conceptual perspective, the present review aimed to provide a novel framework for understanding heterogeneous immunotherapy responses and for designing rational ferroptosis‑based combination strategies.

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Immune network remodeling driven by ferroptosis: Bidirectional interaction mechanisms among multiple immune cells in the lung cancer immune microenvironment (Review)

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