Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality despite recent advances in immunotherapy, particularly with immune checkpoint inhibitors (ICIs). Although ICIs have revolutionized the therapeutic landscape for a subset of patients, durable responses are limited, largely due to complex tumor heterogeneity and an incomplete understanding of immune mechanisms. Traditional tissue-based biomarkers, such as PD-L1 expression and tumor mutational burden (TMB), are constrained by spatial and temporal variability, lack of standardization, and limited predictive precision. Increasingly, attention is turning to minimally invasive, blood-based biomarkers for real-time assessment of immune dynamics. Among these, chemokines and their receptors—especially those detectable on peripheral blood mononuclear cells (PBMCs)—have shown early promise for predicting and monitoring immunotherapeutic outcomes. In parallel, advancements in liquid biopsy and multi-omics platforms now allow for the comprehensive integration of chemokines, circulating tumor DNA (ctDNA), microRNAs, exosomes, and proteomic profiles, forming a more complete portrait of tumor-immune interplay.

This Research Topic aims to advance understanding of the predictive and prognostic utility of chemokine receptors expressed on PBMCs, alongside the integration of emerging multi-omics liquid biopsy biomarkers in non-small cell lung cancer. Central questions include: Which chemokine receptor profiles (such as CXCR4, CXCR6, CXCR3, CCR5, CX3CR1) most effectively anticipate immune checkpoint inhibitor efficacy or resistance? How do these peripheral biomarkers interface with other molecular and proteomic signatures to deliver real-time insights into immune status and tumor response? The overarching goal is to foster research that could yield robust, non-invasive biomarker panels capable of personalizing immunotherapy, improving patient selection, and tracking disease evolution in NSCLC.

The scope of this Research Topic encompasses studies focused on peripheral blood-based chemokine receptor expression and function in NSCLC, as well as their integration with multi-omic biomarkers found in liquid biopsies. Submissions are expected to address both mechanistic and translational aspects, with an emphasis on refining biomarker-driven approaches for immunotherapy personalization.

To gather further insights in biomarker discovery and application in NSCLC immunotherapy, we welcome articles addressing, but not limited to, the following themes:

- Expression and functional significance of chemokine receptors on PBMCs in NSCLC

- Predictive value of chemokine receptor expression for immunotherapeutic outcomes

- Mechanisms of chemokine-mediated immune regulation in the context of lung cancer

- Integration of PBMC-derived biomarkers with established tissue and liquid biopsy signatures (e.g., PD-L1, ctDNA, exosomes)

- Diagnostic, prognostic, and therapeutic strategy development targeting chemokine axes

- Applications of chemokine receptors in molecular imaging (e.g., PET)

- Multi-omics models combining chemokine data with genomic, proteomic, or transcriptomic biomarkers

Appendix: Submissions may include original research articles, systematic reviews, mini-reviews, clinical trial reports, hypothesis and theory papers, and methodological or technical advances.

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Evolving non-invasive biomarkers: Chemokines and multi-omic profiling in NSCLC immunotherapy response