Deciphering the immune heterogeneity dominated by RGS1+ TAMs with prognostic implications and identification of novel immunotherapeutic biomarker CD83 in lung adenocarcinoma

Abstract

Abstract Background Tumor-associated macrophages (TAMs) are a specific subset of macrophages that reside inside the tumor microenvironment (TME). The dynamic interplay between TAMs and tumor cells plays a crucial role in the treatment response and prognosis of lung adenocarcinoma (LUAD). The study aimed to examine the association between TAMs and LUAD to advance the development of targeted strategies and immunotherapeutic approaches for treating this type of lung cancer. Methods The study employed scRNA-seq data to characterize the immune cell composition of LUAD and delineate distinct subpopulations of TAMs. The "BayesPrism" and "Seurat" R packages were employed to examine the association between these subgroups and immunotherapy and clinical features to identify novel immunotherapy biomarkers. Furthermore, a predictive signature was generated to forecast patient prognosis by examining the gene expression profile of RGS1 + TAMs and using 104 machine-learning techniques. Results A comprehensive investigation has shown the existence of a hitherto unidentified subgroup of TAMs known as RGS1 + TAMs, which has been found to have a strong correlation with the efficacy of immunotherapy and the occurrence of tumor metastasis in LUAD patients. CD83 was identified CD83 as a distinct biomarker for the expression of RGS1 + TAMs, showcasing its potential utility as an indicator for immunotherapeutic interventions. Furthermore, the prognostic capacity of RTMscore signature, encompassing three specific mRNA (NR4A2, MMP14, and NPC2), demonstrated enhanced robustness when contrasted against the comprehensive collection of 104 features outlined in the published study. Conclusion The identified RGS1 + TAMs have substantial implications for the treatment and prognosis of LUAD patients.