Biology subjects

Park, G.-H.

Publications and source records attributed to Park, G.-H..

2 recordsLinked to original sources

bioRxiv2024

Systemic CD8+ T cell effector signature predicts prognosis of lung cancer immunotherapy

BackgroundWhile immune checkpoint inhibitors (ICIs) are adopted as standard therapy in non-small cell lung cancer (NSCLC) patients, factors that influence variable prognosis still remain elusive. Therefore, a deeper understanding is needed of how germline variants regulate the transcriptomes of circulating immune cells in metastasis, and ultimately influence immunotherapy outcomes. MethodsWe collected peripheral blood mononuclear cells (PBMCs) from 73 ICI-treated NSCLC patients, conducted single-cell RNA sequencing, and called germline variants via SNP microarray. Determination of expression quantitative trait loci (eQTL) allows elucidating genetic interactions between germline variants and gene expression. Utilizing aggregation-based eQTL mapping and network analysis across eight blood cell types, we sought cell-type-specific and ICI-prognosis-dependent gene regulatory signatures. ResultsOur sc-eQTL analysis identified 3,616 blood- and 702 lung-cancer-specific eGenes across eight major clusters and treatment conditions, highlighting involvement of immune-related pathways. Network analysis revealed TBX21-EOMES regulons activity in CD8+ T cells and the enrichment of eQTLs in higher-centrality genes as predictive factors of ICI response. ConclusionsOur findings suggest that in the circulating immune cells of NSCLC patients, transcriptomic regulation differs in a cell type- and treatment-specific manner. They further highlight the role of eQTL loci as broad controllers of ICI-prognosis-predicting gene networks. The predictive networks and identification of eQTL contributions can lead to deeper understanding and personalized ICI therapy response prediction based on germline variants.

genomics↗

bioRxiv2024

Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden

Clonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICI), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing(scRNA-seq). Whole exome sequencing (WES) was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs 5/42 for controls; P = 0.01). In addition, lung squamous cell carcinoma patients showed increased burden of larger clones compared to lung adenocarcinoma patients (8/43 for LUSC vs 2/50 for LUAD; P = 0.04). Furthermore, single cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-B in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients.

genomics↗