AUTHOR=Yang Maoqin , Lei Xudong , Ren Dexiang , Qin Dakai , Xia Xiaojun 

TITLE=Epigenetic regulation of the tumor microenvironment in lung cancer: mechanism insights and therapeutic prospects

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1697428

DOI=10.3389/fimmu.2025.1697428

ISSN=1664-3224

ABSTRACT=Lung cancer, recognized as one of the most prevalent malignancies with the highest rates of incidence and mortality globally, presents a substantial challenge on a worldwide scale. This challenge is exacerbated by the disease’s difficulty in early detection, a pronounced rate of metastasis, and resistance to treatment, all of which contribute to elevated mortality rates. The tumor microenvironment (TME) plays a critical role in the sustenance and advancement of various solid tumors, including lung cancer. The intricate composition of the TME facilitates tumor proliferation, metastatic spread, and therapeutic resistance by supplying metabolic resources, fostering angiogenesis, and enabling immune evasion. Nonetheless, the regulatory frameworks operating within the TME remain poorly understood. An increasing body of evidence suggests that epigenetic regulation—encompassing mechanisms such as DNA methylation, histone modification, and the action of non-coding RNAs—is pivotal in the initiation and progression of lung cancer. Furthermore, epigenetic modifications significantly influence the functional dynamics of the tumor microenvironment, thereby impacting intercellular interactions and cellular behaviors within the TME, which in turn affects the trajectory of disease progression. This article aims to present the most recent advancements in research concerning the epigenetic regulation of tumor cell interactions with the TME in the context of lung cancer biology. Additionally, it examines the current implications of epigenetic regulation within the tumor microenvironment and its influence on lung cancer behavior. We also investigate the potential relevance and emerging therapeutic avenues presented by epigenetic regulation in the clinical diagnosis and treatment of lung cancer, aspiring to propose novel strategies to address existing treatment challenges.