Characterization of the immune cell infiltration patterns in lung adenocarcinoma to facilitate immunotherapy.

Abstract

Although Immunotherapy has emerged as an efficient treatment in lung carcinoma, merely a subset of lung adenocarcinoma (LUAD) patients could be benefited from it. Increasing evidence revealed that tumor immune cell infiltrating (ICI) in the tumor microenvironment (TME) is highly related to patient prognosis and characteristics of the tumor. Thus far, the immune cell infiltration patterns of LUAD remain unclear. Herein, ESTIMATE and CIBERSORT algorithms were conducted to characterize the ICI patterns of 1155 patients with LUAD. Three ICI subtypes were determined, and the ICI score was constructed by performing PCA. A high ICI score group referred to increased activation of the signaling pathways related to immune activation and drug metabolism, reduced tumor mutation burden (TMB), as well as significantly higher expression levels of CTLA-4, PD-1, LAG3, and immune-activation-related genes. Patients who had high ICI scores showed better overall survival (OS) compared to those with low ICI scores, irrespective of TMB status. This study demonstrated that ICI scores serve as an original and effective indicator for independent prognostic prediction as well as customized immune therapy of LUAD. Establishing the ICI patterns of a larger patient population will extend our knowledg of TME, and it may facilitate the development of immunotherapies specific to LUAD.