Multi-Omics reveals SPP1 + malignant and CXCR4+ TAM crosstalk predicts immunotherapy response in lung adenocarcinoma

BACKGROUND: Lung adenocarcinoma (LUAD), a common lung cancer subtype, is significantly influenced by the immune microenvironment. Immune checkpoint inhibitors have shown limited efficacy in Lung adenocarcinoma due to the immunosuppressive tumor microenvironment (TME). Identifying predictive biomarkers for immunotherapy response remains an urgent clinical need. METHODS: TAM, while in vitro experiments validated the functions of biomarker. RESULTS: TAM, while in vitro experiments demonstrated that CXCR4 plays an important role in the functions of LUAD cells. CONCLUSIONS: This study uncovers the SPP1⁺ malignant and CXCR4⁺ TAM crosstalk as a novel TME-driven resistance mechanism and provides a potential biomarker for stratifying LUAD patients likely to benefit from immunotherapy.