MINI REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Inflammation-driven mechanisms in endometrial cancer: pathways from inflammatory microenvironment remodeling to immune escape
Provisionally accepted
Zhaoping Tan
Binyue ShengLu ChenHong DongYaqin DengYunyun LiCong LiuHan WangZi YangTing XieYanming Huang*- Department of Anaesthesiology, Maternal and Child Health Hospital of Hubei Province, Wuhan, China
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The progression of endometrial cancer (EC) is significantly affected by the inflammatory microenvironment (IME), which is essential for facilitating immune evasion and developing resistance to therapeutic interventions. Components that promote immune suppression, such as regulatory T cells (Tregs), macrophages associated with tumors (TAMs), cytokines like interleukin-10 (IL-10) and transforming growth factors-beta (TGF-β), are crucial in establishing a favourable microenvironment for tumor growth. TAMs with a M2-like phenotype promote angiogenesis and inhibit antitumor immunity through the secretion pro-tumorigenic factor. Further, metabolic shifts in the extracellular matrix and structural modifications of the extracellular matrix (ECM) inhibit the infiltration of cytotoxic T lymphocytes (CTLs), thereby strengthening mechanisms of immune evasion. Inflammatory signaling pathways, such as interleukin-6 /janus kinase /signal transducer and activator of transcription 3 (IL-6/ JAK/ STAT3) and NF-κB / tumor necrosis factor-alpha (TNF-α/NF-κB), also stimulate the expression immune checkpoint molecules, such as programmed cell death protein 1 (PD-1). Novel interventions aimed at modulating immune checkpoints, inhibiting TGF-β signaling, and altering metabolic circuits are under investigation and offer potential to counteract immune suppression and enhance therapeutic success. Nevertheless, significant obstacles remain, including intratumoral heterogeneity, fluctuating immune dynamics, and the absence of dependable biomarkers. Advancements in single-cell analysis and spatial transcriptomics are anticipated to unveil actionable molecular patterns and support the development of individualized strategies to interrupt immune evasion and therapeutic resistance in EC. These advances offer promise for personalized immunotherapy approaches that could significantly improve outcomes in endometrial cancer patients.
Keywords: Endometrial cancer (EC), Inflammatory microenvironment (IME), immune escape, Immune checkpoint blockade, Pembrolizumab–Lenvatinib
Received: 20 Aug 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Tan, Sheng, Chen, Dong, Deng, Li, Liu, Wang, Yang, Xie and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yanming Huang, 389680285@qq.com
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