Ferroptosis Patterns Modulate Immunocyte Communication in Tumor Microenvironments: Clinical Value and Therapeutic Guidance of Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) emerges as one of the most aggressive tumor types with a poor prognosis. As a novel form of regulated cell death, ferroptosis promotes the clearance of tumor cells. However, few studies demonstrated whether ferroptosis-related genes can modify the behavior of tumor microenvironment (TME) cells. Resorting to non-negative matrix factorization (NMF) clustering based on the expression of ferroptosis-related genes, we identified multiple LUAD TME cell-type subpopulations. These subtypes of TME cells displayed extensive communication with tumor epithelial cells. ATF3+cancer-associated fibroblasts (CAFs), SLC40A1+CD8+T cells, and ALOX5+CD8+T cells showed distinct biological features compared to non-ferroptosis-related TME cells. Patients with a higher abundance of these ferroptosis-related TME cell subtypes showed a favorable clinical outcome. Our study depicted a detailed landscape of LUAD cell composition with a focus on ferroptosis-related genes, which, hopefully, may provide novel insight into further study of the LAUD immune microenvironment.