Correlation analysis of m⁶A-modified regulators with immune microenvironment infiltrating cells in lung adenocarcinoma

by Wei Ye, Tianpeng Huang

Recent studies have demonstrated the epigenetic regulation of immune responses. However, the potential role of N6-methyladenosine methylation (m⁶A) in the tumor microenvironment (TME) remains unknown.

In this study, the m⁶A 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 m⁶A score was constructed using the principal component analysis algorithm to quantify the m⁶A modification mode of a single tumor.

There were three distinct patterns of m⁶A 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 m⁶A scores were characterized by immune activation and poor survival rate. Besides, m⁶A 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 m⁶A scores demonstrated significant therapeutic advantages and clinical benefits. m⁶A modifications play an important role in the development of TME diversity. Assessing the m⁶A modification pattern of individual tumors can deepen the understanding as to the characteristics of TME infiltration and guide more effective immunotherapy strategies.