Abstract A144: Association of CC chemokine receptor 5 (CCR5) and its natural ligands in lung cancer disparity

Abstract Background: Lung cancer is the leading cause of cancer-related deaths in the United States, with a five-year survival rate of only 28%. African Americans (AAs) experience a disproportionately higher incidence and lower survival rates compared to other populations, suggesting that differences in the molecular landscape contribute to these disparities. This study establishes the association of CC chemokine receptor type 5 (CCR5) with lung cancer disparities. Initial results indicated higher CCR5 expression in lung cancer cell lines derived from African American patients compared to those from European American (EA) patients. Methods: A transcriptomic approach was used to determine the expression association of CCR5 with lung cancer-related genes in cell lines derived from AA and EA. Total RNA isolated from these cells was sequenced with ∼50 million reads per strand using a 300 bp paired-end protocol on an Illumina platform. HISAT2 for gene-level analysis and Salmon for transcript-level mapping were used for sequence assembly. Differential expression analysis was performed between groups with DESeq2 for statistical significance. To determine the biological relevance of CCR5, cell migration, and cell proliferation assays were performed using trans-well systems, MTT, and BrdU with or without activating CCR5. Group comparisons were evaluated through t-tests and Kruskal-Wallis analysis using GraphPad Prism. Results: Our data indicate higher CCR5 transcripts (1010.75 vs. 225.25 TPM) in cell lines derived from African Americans (AA) compared to European Americans (EA). Transcripts of CCL5 (1,348,670.05 vs. 1,477,699 TPM). Furthermore, in response to CCL5, a natural ligand of CCR5, our data shows activation of distinct oncogenic pathways in cell lines derived from AA compared to EA. Functional studies show higher migratory behavior in AA cell lines in response to CCL5 chemotactic gradient compared to EA. Treatment with maraviroc (MVC), a CCR5 inhibitor, resulted in a significant reduction (p<0.0001) in cell proliferation across all cell lines, regardless of their origin. This suggests that critical role of CCR5 in lung cancer disparity and targeting CCR5 holds promise to reduce the observed disparities in treatment and disease outcome. Conclusion: This suggests the critical role of CCR5 in lung cancer disparity and targeting CCR5 holds promise to reduce the observed disparities in treatment and disease outcome. Citation Format: Briana A. Brock, Murugesh Eswaran, Hina Mir, Shailesh Singh. Association of CC chemokine receptor 5 (CCR5) and its natural ligands in lung cancer disparity [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A144.