Targeting tumor-associated macrophages-induced IGF1/PI3K/Zic1 axis triggers SHH medulloblastoma regression and chemosensitization - PubMed
7 hours ago
- #chemoresistance
- #medulloblastoma
- #tumor-associated macrophages
- Tumor-associated macrophages (TAMs) play a significant role in medulloblastoma (MB) progression and chemoresistance.
- Depletion of M2-like TAMs, either genetically or pharmacologically, downregulates Zic1 expression and impedes MB growth.
- M2-like TAMs secrete IGF1, activating the PI3K/mTOR/Zic1 axis in MB cells, which contributes to chemoresistance.
- Combining CSF1R inhibitor PLX3397 with chemotherapy reduces M2-like TAMs infiltration and attenuates the IGF1/PI3K/Zic1 signaling axis.
- This combination strategy synergistically inhibits tumor growth and extends survival in mice, suggesting a potential treatment for SHH MB.