MINI REVIEW article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Soluble Cytokines and Chemokines in NSCLC: Drivers of Immune Evasion and Angiogenesis
Liang Yang 1
Zhijun Fan 2
Dong Zhou 2
Zhe Wang 2
1. Department of Radiotherapy, Affiliated Zhongshan Hospital of Dalian University, Liaoning, Dalian 116001, China, Dalian, China
2. Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Liaoning, Dalian 116001, China, Dalian, China
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Abstract
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. The tumor microenvironment (TME) is characterized by a dynamic network of soluble cytokines and chemokines that orchestrate immune evasion, promote angiogenesis, and facilitate metastatic dissemination. Among these, interleukins such as IL-6, IL-8, and IL-10, along with chemokine axes including CXCL12–CXCR4 and CCL21–CCR7, are critical drivers of tumor progression and resistance to immunotherapy. These mediators modulate immune cell recruitment, epithelial– mesenchymal transition, and vascular remodeling, thereby shaping tumor behavior and therapeutic response. In parallel, angiogenic factors such as VEGF, bFGF, and MMPs promote neovascularization and extracellular matrix degradation, reinforcing metastatic potential. Notably, cytokine signatures in peripheral blood are emerging as prognostic biomarkers and predictive indicators for immune checkpoint blockade efficacy, particularly PD-1 inhibitors. This review systematically summarizes the current understanding of soluble mediator-driven mechanisms in NSCLC progression, including cytokines and chemokines, providing new opportunities for biomarker-guided precision therapy and combination strategies in NSCLC.
Summary
Keywords
Angiogenesis, chemokine, cytokine, Immunotherapy, metastasis, Non-small cell lung cancer, PD-1, Soluble Mediator
Received
04 September 2025
Accepted
19 February 2026
Copyright
© 2026 Yang, Fan, Zhou and Wang. 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: Dong Zhou; Zhe Wang
Disclaimer
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