Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities

Table 3 Summary of selected BM therapy strategy targeting glial cells

Targeting	Application	Tumor type	Objects	Status	Ref.
Astrocytes
STAT3	Silibinin	Human and mouse BM cell lines, lung cancer	Mice model, Human Patients	Published in 2018	[81]
	Silibinin	NSCLC, BC	Clinical trial	Recruiting	NCT05689619
	WBRT + silibinin	BM, LC	Clinical trial	Recruiting	NCT05793489
Gap junction	carboplatin + meclofenamate/tonabersat	TNBC, NSCLC	Mice model	Published in 2016	[84]
	T-M/siRNA	BC	Mice model	Published in 2022	[201]
	Meclofenamate	Solid tumor	Clinical trial	Active, non-recruiting	NCT02429570
Microglia/Macrophages
MRC1 + cells	Mannosylated clodronate liposomes	BC	Mice model	Published in 2017	[28]
PI3K	BKM120	BC	Mice model	Published in 2018	[94]
TLR9	CpG-C*	Lung cancer, melanoma	Mice model	Published in 2019	[205]
CSF1R	PLX3397	BC	Mice model	Published in 2021	[202]
	BLZ945 + AC4-130 (CSF2Rβ-STAT5 inhibitor)	BC	Mice model	Published in 2021	[203]
Estrogen-STAT3	Tamoxifen	BC	Mice model	Published in 2021	[204]
IL6-JAK2-STAT3	Fedratinib (JAK2 inhibitor), tocilizumab (anti-IL6R)	NSCLC	Mice model	Published in 2022	[89]

BM, brain metastases; NSCLC, non-small cell lung cancer; BC, breast cancer; TNBC, triple-negative breast cancer; LC, leptomeningeal carcinomatosis; STAT, signal transducer and activator of transcription; MRC1, mannose receptor 1; PI3K, phosphoinositide 3-kinase; TLR9, Toll-like receptor 9; CSF1R, colony-stimulating factor 1 receptor; CSF2Rβ, colony-stimulating factor 1 receptor beta; IL6, interleukin 6; JAK2, Janus kinase 2
*The agonist, the others are inhibitors

ISSN: 1756-8722