# TMT1A inhibits lung adenocarcinoma progression by suppressing M2 macrophage polarization

## TL;DR

TMT1A suppresses lung cancer growth by reducing M2 macrophage polarization and boosting immune cell activity.

## Contribution

TMT1A is identified as a tumor suppressor and immune modulator in lung adenocarcinoma.

## Key findings

- TMT1A downregulation is linked to poor lung adenocarcinoma prognosis.
- TMT1A inhibits cancer cell proliferation and migration.
- TMT1A blocks M2 macrophage polarization and enhances CD8+ T cell activation.

## Abstract

The role of thiol methyltransferase 1A (TMT1A) in lung adenocarcinoma (LUAD) progression and the immune microenvironment remains unclear. Analysis of clinical samples and public databases revealed significantly lower TMT1A expression in tumorous LUAD samples compared to 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 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-γ 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.

•TMT1A downregulation predicts poor prognosis in lung adenocarcinoma•TMT1A inhibits LUAD cell proliferation, migration, and invasion•TMT1A blocks M2 macrophage polarization and enhances CD8+ T cell activation

TMT1A downregulation predicts poor prognosis in lung adenocarcinoma

TMT1A inhibits LUAD cell proliferation, migration, and invasion

TMT1A blocks M2 macrophage polarization and enhances CD8+ T cell activation

Immunology; Cancer