Fig. 1

Mechanism of brain metastasis and the timeline for progress in immunotherapy. (A) Circulating tumor cells or metastatic cells predispose the primary melanoma, lung, breast, renal, and colorectal cancers to enter the bloodstream or systemic circulation through intravasation, reach to the brain, and extravasate through the blood-brain barrier. In the brain, these metastatic cells evade apoptosis through L1CAM mediated vascular co-option, and various other factors such as STAT3, PI3K, S6GALNAC5, and cathepsin S help these cells to colonize and grow. These cells also modify their metabolism to high OXPHOS and become less glycolytic. (B) Timeline progress related to the implications of various immunotherapies in treating brain metastasis.