Major mechanisms underlying brain metastasis. Circulating tumor cells (CTCs) cross the blood–brain barrier (BBB) via
extravasation after BBB disruption. Subsequently, the tumor microenvironment is reestablished
through angiogenesis and reprogrammed immunity. Metastatic cancer cells produce
molecules, such as miRNAs and immunosuppressive factors, that help them
communicate and adapt to the brain environment. (A) Metastatic cancer
cells reprogram adaptive immunity through the PD1/PD-l1 and CTLA4/CD80 immune checkpoints, leading to immune evasion and
immunosuppression. (B) Astrocytes, cancer cells, and microglia interact with each other through the secretion of chemokines and cytokines. Activated STAT3,
NF-κB, AKT-MAPK pathways in cancer cells lead to tumor proliferation and
growth. CCL2 and CCL10, which are secreted by metastatic
cancer cells, recruit more
immunosuppressive microglia. (C) c-Met, RAGE, and VEGF overproduced by
M2 microglia promote tumor angiogenesis. (D) Interactions between
metastatic cancer cells, microglia, and T cells promote immune escape. Exosomal miRNAs contribute to microglial M2 polarization, which promotes
cancer cell colonization and inhibits the cytotoxic effects of T-cells through the secretion
of immunosuppressive cytokines.
Pubdate： 2024-02-23
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