Fig. 3

A APCs first identify antigens from intracranial and primary lesions, then translocate to cervical or adjacent lymph nodes, where the APCs activate T cells by presenting these antigens. Meanwhile, ICIs activate exhausted T cells by blocking the interaction between the checkpoints and the ligands. The BBB is a physical barrier made of endothelial cells with tight cell-to-cell junctions. The extravascular CTLs finally traverse through the BBB through a series of leukocyte-endothelial cell contacts and matrix metalloprotease secretion and enter the brain metastatic location. B Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress produced by irradiated tumor cells promote the exposure or release of damage-associated molecular patterns. On irradiation of tumor cells, PD-L1 expression is seen to have significantly increased. C Due to the radio-responsiveness of both the surrounding oligodendrocytes and endothelial cells, irradiation can mildly but effectively disrupt the BBB/BTB and enhance permeability. Additionally, radiation enhanced the proportion of dendritic cells and activated T cells in brain metastases