KYNU in macrophages contributes to the unique immune feature of LUAD via integrating single-cell and bulk RNA sequencing data: an exploratory analysis

by Jie Yao, Changshuai Zhou, Liren Ding

Background Lung adenocarcinoma (LUAD) is a predominant subtype of lung cancer associated with an unfavorable prognosis. However, the roles of the tumor microenvironment (TME) and Kynureninase (KYNU) in LUAD remain largely unclear. This study aimed to investigate the potential role of KYNU in macrophages and LUAD.

Methods All LUAD related data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression of KYNU was analyzed across different cell types following dimensionality reduction analysis. Immune cell infiltration and immunotherapy response prediction were performed using CIBERSORT and TIMER, respectively. Gene set variation analysis (GSVA) was employed for functional enrichment.

Results Among all immune cells in LUAD, KYNU was primarily expressed in monocytes and macrophages. The upregulated genes in KYNU+macrophages group were significantly enriched in in gene ontology (GO) terms related to antigen processing and presentation. There were increased MHC-I/ MHC-II signal interactions between KYNU+macrophages and B cells as well as T cells. In LUAD patients with higher proportions of KYNU+macrophages, a significantly greater number of patients benefited from immunotherapy (p = 0.033). GSVA results indicated that the MHC pathway was significantly activated in high KYNU+macrophage group.

Conclusions KYNU is primarily in LUAD macrophages, contributing to the distinct immune features and correlating with the enhanced antigen presentation in LUAD. This study preliminarily confirms that KYNU may serve as a potential biomarker for immunotherapy.