Unveiling the immunomodulatory dance: endothelial cells’ function and their role in non-small cell lung cancer - review

Sep 23, 2026

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The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment are central to non-small cell lung cancer (NSCLC) progression. Endothelial cells display diverse immunomodulatory capabilities, shaping immune recruitment, antigen presentation, and the control of immune checkpoint expression. Clarifying the multiple roles of TECs and mapping distinct functional hallmarks across TEC phenotypes can enable more precise therapeutic development. The review explores TEC–immune interplay and discusses optimized treatment opportunities within advanced immunotherapy and anti-angiogenic strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Tumor microenvironment and endothelial specialization

Single-cell characterization of NSCLC TME

Tumor endothelial cells and anti-angiogenic therapy

Rationale for deeper analysis of tumor endothelium

Review focus and therapeutic implications

Daum etal. Molecular Cancer (2025) 24:21 [https://doi.org/10.1186/s12943-024-02221-6](https://doi.org/10.1186/s12943-024-02221-6) Molecular Cancer REVIEW Open Access Unveiling the immunomodulatory dance: endothelial cells’ function and their role in non-small cell lung cancer Sophia Daum 1†, Lilith Decristoforo 1†, Mira Mousa2, Stefan Salcher 1, Christina Plattner3, Baharak Hosseinkhani4, Zlatko Trajanoski3, Dominik Wolf1, Peter Carmel iet2,4 and Andreas Pircher 1* Abstract The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment play a critical role in the progression of non-small cell lung cancer (NSCLC) . In general, endothelial cells exhibit diverse immunomodulatory properties, influencing immune cell recruitment, antigen presentation, and regulation of immune checkpoint expression. Understanding the multifaceted roles ofTECs as well as assigning specific functional hallmarks to various TEC phenotypes offer new avenues for targeted development of therapeutic interventions, particularly in the context of advanced immunotherapy and anti-angiogenic treatments. This review provides insights into the complex interplay between TECs and the immune system in NSCLC including discussion of potential optimized therapeutic opportunities. Keywords NSCLC, Endothelium, TEC, Lung, Angiogenesis, Immune response, Vessel, TME, Therapy, Cancer †Sophia Daum and Lilith Decristoforo contributed equally to this work. *Correspondence: Andreas Pircher [andreas.pircher@i-med.ac.at](andreas.pircher@i-med.ac.at) 1Internal Medicine 5, Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Tyrolean Cancer Research Institute (TKFI), Medical University Innsbruck, Innsbruck, Austria 2Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates 3Institute of Bioinformatics, Biocenter Medical University Innsbruck, Innsbruck, Austria 4Laboratory ofAngiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), VIB Center for Cancer Biology, KU Leuven, VIB, Leuven, Belgium Introduction Recent advances in the understanding of the tumor microenvironment (TME) and deep genetic characterization of non-small cell lung cancer (NSCLC) paved the way for the development of targeted therapies and novel treatment strategies. The effectiveness of these advancements, underscored by the application of immuno-and anti-angiogenic therapies, is designed to tackle the complexities inherent in the TME. Nevertheless, NSCLC remains the leading cause of cancer-related mortality worldwide [1]. The lung, being a highly vascularized organ, provides a unique microenvironment with specialized endothelial cells (ECs), that show heightened expression of genes related to immune regulation, particularly those involved in leukocyte cell-to-cell adhesion, T cell activation, and leukocyte migration [2]. High-resolution in-depth characterization of the TME, including the identification and analysis of various cell types and their subpopulations, © The Author(s) 2025. 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

FAQs

Why are tumor endothelial cells (TECs) important in NSCLC?

TECs help promote tumor growth and act as a critical therapeutic target in NSCLC, supported by the role of anti-angiogenic therapy and broader evidence of TEC immunogenic features.

How do endothelial cells influence the immune microenvironment?

Endothelial cells exhibit immunomodulatory properties that affect immune cell recruitment, antigen presentation, and regulation of immune checkpoint expression, thereby shaping immune responses in NSCLC.

What limits the effectiveness of anti-angiogenic therapy in NSCLC?

Its effectiveness is often transient, with primary or secondary resistance mechanisms reducing long-term efficacy, motivating more comprehensive approaches to understand TEC-related challenges.

Sep 23, 2026

Uploaded by Himbo