What question did this study set out to answer?

The research aims to investigate how variations in the CCL20 ligand contribute to disparities in non-small cell lung cancer incidence and outcomes among ethnic groups.

April 5, 2026

Abstract 1507: Health behavior associated CCL20 ligand variation contributes to the disparity in non-small cell lung cancer

Key Points

The research aims to investigate how variations in the CCL20 ligand contribute to disparities in non-small cell lung cancer incidence and outcomes among ethnic groups.
Analyzed bulk RNA-seq data from lung cancer cell lines of African American and European American origins.
Conducted molecular dynamics simulations to assess CCL20's interaction with the CCR6 receptor.
Compared downstream signaling pathways linked to oncogenic outcomes and smoking behaviors among different populations.
Isoform-2 of CCL20 exhibited stronger interactions with CCR6 in African American cells compared to European American cells.
African American smokers showed higher levels of CCL20 Isoform-2 compared to non-smokers and European American smokers.
Molecular dynamics indicated Isoform-2 has the highest binding affinity for CCR6, suggesting it is a key activator in signaling.

Abstract

Abstract Background: Lung cancer exhibits disparities in incidence, disease prevalence, and treatment outcomes. Chemokines and their corresponding receptors have been shown to be associated with these observed disparities within different ethnic groups. In this study, we have demonstrated that the differential signaling of chemokine receptor CCR6 and its natural ligand is associated with the observed disparity, and this differential CCR6 signaling is primarily due to the diversity in CCL20. Methods: Bulk RNA-seq data (BioProject ID: PRJNA1039495) from lung cancer cell lines derived from African American (AA) and European American (EA) individuals were analyzed to identify and quantify different isoforms of CCL20. MD simulations were performed to evaluate the binding affinity of CCL20, hydrogen-bond stability, and conformational behavior upon interaction with the CCR6 receptor. Downstream pathway activation potential was inferred by comparing the expression of signaling molecules that support oncogenic pathways and are associated with poor therapeutic outcomes. Furthermore, smoking habits, including higher nicotine intake, distinct metabolite patterns, and alterations in basic cytokine levels, were incorporated into the model as external factors that may influence CCL20 isoforms and CCR6 signaling. Results: Out of 5 CCL20 isoforms, Isoform-1 (24 TPM) and Isoform-2 (36 TPM) showed stronger interactions with CCR6 compared to EA cells (Isoform-1: 7.5 TPM; Isoform-2: 11.2 TPM). Across smoking groups, AA cells showed higher Isoform-2 levels than EA cells, increasing from non-smokers (Isoform-1: 18 TPM; Isoform-2: 18 TPM) to smokers (Isoform-1: 24 TPM; Isoform-2: 40 TPM), while EA cells showed lower increases from non-smokers (Isoform-1: 18 TPM; Isoform-2: 19 TPM) to smokers (Isoform-1: 24 TPM; Isoform-2: 30 TPM). MD simulations revealed that lung-cancer-cell CCR6 binds both CCL20 Isoform-1 Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1507.

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Cite This Study

Eswaran et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fe07a79560c99a0a46fb https://doi.org/https://doi.org/10.1158/1538-7445.am2026-1507

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