TMT1A inhibits lung adenocarcinoma progression by suppressing M2 macrophage polarization
The involvement of human Thiol Methyltransferase 1A (TMT1A) protein has been reported in the development of several tumors. However, its role in tumor progression and immune microenvironment of lung adenocarcinoma (LUAD) has not been fully elucidated. Analysis of clinical samples and public databases revealed significantly lower TMT1A expression in tumorous LUAD samples as opposed to their non-neoplastic counterparts. Cox regression analysis confirmed TMT1A as an independent prognostic factor for LUAD. Phenotypically, functional assays demonstrated that TMT1A expression inhibited LUAD cell proliferation, cell-cycle progression, invasion and migration. Furthermore, single cell transcriptome sequencing analysis showed that TMT1A expression was positively correlated with the immune cells, especially macrophages. Mechanistically, high TMT1A expression was found to inhibit M2 macrophage polarization and downregulate PD-L1 expression in LUAD cells. In co-culture experiments involving LUAD cells and T cells, TMT1A knockdown suppressed T cell activation and reduced IFN-gamma secretion. These findings were further validated by in vivo experiments, where TMT1A expression was found to promote CD8+ T cell infiltration in LUAD. These findings demonstrated tumor-suppressive functions coupled with its immunomodulatory capacity position TMT1A as a promising therapeutic target for LUAD treatment.