Growing evidence implies a link between DNA methylation and
tumor immunity/
immunotherapy. However, the global influence of DNA methylation on the characteristics of the tumor microenvironment and the efficacy of
immunotherapy remains to be clarified. In this study, we systematically evaluated the DNA methylation regulator patterns and tumor microenvironment characteristics of 1,619
gastric cancer patients by clustering the gene expression of 20 DNA methylation regulators. Three
gastric cancer subtypes that had different DNA methylation modification patterns and distinct tumor microenvironment characteristics were recognized. Then,
a DNA methylation score (DMS) was constructed to evaluate DNA methylation modification individually. High DMS was characterized by immune activation status, increased
tumor mutation burden, and
tumor neoantigens, with a favorable prognosis. Conversely, activation of the stroma and absence of immune cell infiltration were observed in the low DMS group, with relatively poor survival. High DMS was also certified to be correlated with enhanced efficacy of
immunotherapy in four immune checkpoint blocking treatment cohorts. In conclusion, the characterization of DNA methylation modification patterns may help to enhance our recognition of the
tumor immune microenvironment of
gastric cancer and guide more personalized
immunotherapy strategies in the future.