2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.09 Single Cell RNA Sequencing and Functional Monocyte Stimulation Reveals Phenotypic Predispositions to Developing Lung Cancer in Never Smokers

P1.03D.09 Single Cell RNA Sequencing and Functional Monocyte Stimulation Reveals Phenotypic Predispositions to Developing Lung Cancer in Never Smokers

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The study utilizes single-cell RNA sequencing and functional monocyte stimulation to explore potential phenotypic predispositions for developing lung cancer in never-smokers (LCINS). While 20% of men and 50% of women with lung cancer have never smoked, research on risk factors specific to this group is limited. One significant finding in previous research shows that interleukin 1-beta (IL1B) secretion by macrophages in response to pollution exposure is crucial in the development of LCINS.<br /><br />The study aimed to understand genetic differences in inflammatory genes that may predispose individuals to lung cancer. It utilized expression quantitative trait loci (eQTLs) at the cellular level applied to vital genes in the chronic inflammatory response. The investigatory approach included a reference dataset from the OneK1K project, consisting of single immune cell profiles from 1,000 healthy individuals.<br /><br />Methodologically, peripheral blood mononuclear cells (PBMCs) from LCINS patients and age-matched healthy never-smoking controls were analyzed. A total of 50,000 cells from cancer patients and 330,000 cells from controls were sequenced and analyzed for eQTL associations. The study identified 294 eQTLs across 77 inflammatory genes in 20 immune cell types, with IL1B exhibiting differential expression according to single nucleotide polymorphism (SNP) genotype across all tested monocyte populations.<br /><br />Furthermore, a functional monocyte assay demonstrated IL1B's response to inflammatory stimuli, indicating the potential for identifying at-risk populations through monocyte IL1B expression associated with IL1B SNPs. This research provides a foundational understanding of the genetic and inflammatory pathways predisposing individuals to lung cancer in the absence of traditional smoking-related risk factors.

Asset Subtitle

Venessa Chin

Meta Tag

Speaker Venessa Chin

Topic Tumor Biology – Translational Biology

Keywords

single-cell RNA sequencing

lung cancer in never-smokers

LCINS

interleukin 1-beta

IL1B

expression quantitative trait loci

eQTLs

inflammatory genes

monocytes

pollution exposure