| Description |
This study delved into this inquiry through single-cell RNA sequencing and other experimental validations on cerebrospinal fluid (CSF) for EGFR-mutant NSCLC with central nervous system metastases. Our findings revealed a striking functional and phenotypic heterogeneity in macrophages of LM, accompanied by heightened immunosuppressive attributes. Of utmost significance, a distinctive subset of lipid-associated macrophages (RNASE1_M) within CSF was associated with both Osimertinib resistance and the progression of LM. Furthermore, we proposed that these particular macrophages were potentially regulated by Midkine (MDK), validated as a prognostic biomarker for LM in CSF. In addition, our study illustrated that these macrophages might contribute to immune evasion through CD47-SIRPA interactions between epithelial cells and macrophages. Collectively, our findings provided novel insights into CSF macrophages' role in Osimertinib resistance and LM progression, presenting promising avenues to combat Osimertinib resistance and mitigate LM. |
