Surgical intervention strategies for tumor microenvironment (TME) associated therapeutic resistance - Review

Sep 29, 2026

The tumor microenvironment (TME) drives therapeutic resistance through immunosuppression, stromal remodeling, and metabolic reprogramming, creating major barriers in solid tumor care. Although surgery is central to tumor eradication, perioperative inflammation and ischemia-reperfusion injury can worsen TME deterioration. This narrative review analyzes TME components and resistance mechanisms and proposes a multi-stage surgical intervention framework spanning preoperative reshaping, intraoperative precision resection with local therapy, and postoperative dynamic monitoring.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Composition and function of the TME

Cellular components

Cancer-associated fibroblasts (CAFs)

Chen et al. Discover Oncology (2026) 17:18 [https://doi.org/10.1007/s12672-025-04092-9](https://doi.org/10.1007/s12672-025-04092-9) Discover Oncology REVIEW Open Access Surgical intervention strategies for tumor microenvironment (TME) associated therapeutic resistance Dong Chen1, Hanyu Wang1 and Xu Che1* *Correspondence: Xu Che gandan-chendong@cicams-sz. [org.cn](org.cn) 1National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital & Shenzhen Hospital,, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China Abstract The tumor microenvironment (TME) drives therapeutic resistance through immunosuppression, stromal remodeling, and metabolic reprogramming, which posea major challenge in solid tumor treatment. While surgery remains a cornerstone for tumor eradication, perioperative inflammatory responses and ischemia-reperfusion injuries may exacerbate TME deterioration. However, surgery also offers a strategic opportunity for TME modulation. This narrative review analyzes TME components and resistance mechanisms, proposing a multi-stage intervention framework: preoperative TME reshaping, intraoperative precision resection with local therapy, and postoperative dynamic monitoring. We further explore a multidisciplinary wholecourse management model, integrating cutting-edge technologies such as radiomicsand single-cell sequencing. By bridging basic research with clinical translation, this review aims to guide surgeons in transitioning from tumor resection to TME precision regulation, with a focus on perioperative multi-stage interventions. Keywords Tumor microenvironment, Therapeutic resistance, Surgical intervention, Multidisciplinary collaboration 1 Introduction The TME is a highly dynamic and complex ecosystem, composed of tumor cells, immune cells, stromal cells, the extracellular matrix (ECM), cytokines, and various other components. Its remarkable heterogeneity and plasticity are the root causes of resistance to chemotherapy, radiotherapy, and immunotherapy in cancer treatment [1]. Although surgical resection is a primary approach for removing solid tumors, the surgical trauma can trigger a cascade of events, including inflammatory reactions, hypoxic stress, and immunosuppression. These responses may inadvertently create a more favorable environment for the invasion and metastasis of residual tumor cells. For instance, studies have demonstrated that the release of interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) following surgery can activate the STAT3 pathway, leading to epithelial-mesenchymal transition (EMT) in tumor cells. This enables them to acquire invasive properties, and promotes the expansion of cancer stem cells (CSCs), which are highly © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by-nc-nd/4.0/. Chen et al. Discover Oncology (2026) 17:18 Page 2 of 12 resistant to conventional therapies. Consequently, this sign

FAQs

How does the tumor microenvironment contribute to therapeutic resistance?

The TME promotes resistance via immunosuppression, stromal remodeling, and metabolic reprogramming, driven by heterogeneity and plasticity that reduce treatment effectiveness.

What perioperative events can worsen the tumor microenvironment after surgery?

Surgical trauma can trigger inflammatory reactions, hypoxic stress, and immunosuppression, which may create a more favorable niche for invasion and metastasis of residual tumor cells.

What multi-stage intervention framework does the review propose?

The review proposes preoperative TME reshaping, intraoperative precision resection with local therapy, and postoperative dynamic monitoring, aiming to modulate the TME and overcome resistance.

Sep 29, 2026

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