Soluble cytokines and chemokines in NSCLC: drivers of immune evasion and angiogenesis

TL;DR

This paper reviews how soluble cytokines and chemokines in non-small cell lung cancer influence immune evasion, angiogenesis, and treatment resistance.

Contribution

The paper systematically summarizes soluble mediator-driven mechanisms in NSCLC progression and their therapeutic implications.

Findings

Cytokines like IL-6, IL-8, and IL-10 drive tumor progression and resistance to immunotherapy.

Chemokine axes such as CXCL12–CXCR4 and CCL21–CCR7 modulate immune cell recruitment and metastasis.

Cytokine signatures in blood can serve as biomarkers for predicting immunotherapy response.

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.

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