Correlation analysis of m(6)A-modified regulators with immune microenvironment infiltrating cells in lung adenocarcinoma

OBJECT: Recent studies have demonstrated the epigenetic regulation of immune responses. However, the potential role of N6-methyladenosine methylation (m(6)A) in the tumor microenvironment (TME) remains unknown. METHOD: In this study, the m(6)A modification patterns of LUAD samples were comprehensively evaluated by combining TCGA and GEO data, while these modification patterns were systematically linked to the characteristics of immune infiltrating cells in TME. The m(6)A score was constructed using the principal component analysis algorithm to quantify the m(6)A modification mode of a single tumor. RESULT: There were three distinct patterns of m(6)A modification identified. The characteristics of TME cell infiltration in these three patterns were highly consistent with these three immune phenotypes of the tumors, including immune rejection, immune-inflammatory, and immune inert phenotypes. Low m(6)A scores were characterized by immune activation and poor survival rate. Besides, m(6)A scores were associated with tumor mutational load (TMB) and were able to increase the ability of TMB to predict immunotherapy. Two immunotherapy cohorts confirmed that the patients with lower m(6)A scores demonstrated significant therapeutic advantages and clinical benefits. m(6)A modifications play an important role in the development of TME diversity. Assessing the m(6)A modification pattern of individual tumors can deepen the understanding as to the characteristics of TME infiltration and guide more effective immunotherapy strategies.