Deciphering macrophage heterogeneity and factors driving M2 polarization in lung adenocarcinoma through single-cell RNA sequencing.

Immune checkpoint inhibitors (ICIs) have shown promise in enhancing non-small cell lung cancer (NSCLC) patient prognoses, but their effectiveness is contingent upon the specific tumor microenvironment (TME). In this research, we examined the heterogeneity and plasticity of tumor-associated macrophages in lung adenocarcinoma (LUAD) using single-cell sequencing data GSE207422, identifying genes that may influence their polarization. We identified a positive correlation between BCAT1 expression in immune-resistant patient tissues and M2 macrophage infiltration. Pseudo-temporal analysis revealed a significant overlap between BCAT1 expression dynamics and the trajectory of macrophage M2 polarization. Evidence from both in vitro and in vivo studies indicated that BCAT1 might foster an immunosuppressive environment by driving M2 macrophage polarization, which could account for the aggressive spread of LUAD and suboptimal responses to immunotherapy. Overall, our findings flagged BCAT1-high-expressing macrophages as a suppressive element in the TME, hinting that targeting BCAT1 could shift macrophage polarization and enhance patient outcomes.