| Autor: |
Yang-Si Li, Wen-Pu Lai, Kai Yin, Mei-Mei Zheng, Hai-Yan Tu, Wei-Bang Guo, Liang Li, Shou-Heng Lin, Zhen Wang, Lu Zeng, Ben-Yuan Jiang, Zhi-Hong Chen, Qing Zhou, Xu-Chao Zhang, Jin-Ji Yang, Wen-Zhao Zhong, Xue-Ning Yang, Bin-Chao Wang, Yi Pan, Hua-Jun Chen, Fa-Man Xiao, Hao Sun, Yue-Li Sun, Xiao-Yan Bai, E.-E. Ke, Jia-Xin Lin, Si-Yang Maggie Liu, Yangqiu Li, Oscar Junhong Luo, Yi-Long Wu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 43, Iss 8, Pp 114613- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114613 |
| Popis: |
Summary: Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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