183P Identification of an antigen-presenting cells/T/NK cells-related gene signature to predict prognosis and gene marker CTSL to predict immunotherapeutic response for lung adenocarcinoma: An integrated analysis of bulk and single cell RNA sequencing

Background: Antigen-presenting cells (APC)/T/NK cells are key immune cells that play crucial roles in fighting against malignancies including lung adenocarcinoma (LUAD).In this study, we aimed to identify an APC/T/NK cell-related gene signature (ATNKGS) and potential immune marker genes (IMGs) to realize risk stratification, prognosis and immunotherapeutic response prediction for LUAD patients.Methods: Based on 196 antigen-presenting cells (APC)/T/NK cellsrelated genes collected from three pathways in the Kyoko encyclopedia of genes and genomes (KEGG) database, we determined the final genes and established the ATNKGS-related risk model via univariate Cox regression and LASSO Cox regression.Then we correlated ATNKGS with overall survival (OS), clinical characteristics, immune cell infiltration, and functional enrichment analysis of LUAD patients.The single cell RNA sequencing data was applied for identification of key IMGs and investigate their value in immunotherapeutic response prediction.Results: In this study, 8 independent public datasets including 1089 patients were enrolled.An ATNKGS containing 16 genes was constructed for prognostic prediction of overall survival in the TCGA discovery dataset.Its prognostic capability was verified by TCGA validation dataset and four other GEO datasets.A nomogram combining ATNKGS risk score and clinical TNM stage maximized the survival prediction of LUAD.The single cell RNA sequencing analysis revealed CTSL and HSPA6 as the key IMGs for monocyte and dendritic cells, respectively.Moreover, though CTSL was an indicator for poor prognosis of LUAD patients, CTSL high expression group was associated with higher ESTIMATEScore, immune checkpoints expression, and lower TIDE score.Several immunotherapeutic cohorts have confirmed the response-predicting significance of CTSL in patients receiving ICI treatment.Conclusions: In conclusion, our study provided an insight into the significant role of APC/T/NK cells-related genes in survival risk stratification and CTSL in response prediction of immunotherapy in patients with LUAD.