MAP2K7 and osteosarcoma: Endothelial ICAM-1/VCAM-1 merit inclusion because NGF–TrkA–MEK/ERK–AP-1 increases these molecules, while ACh/α7nAChR signaling can restrain their expression and tune nitric-oxide–dependent vascular tone in bone, jointly shaping effector T-cell entry and response to ICB; analogous mechanisms are testable in osteosarcoma using quantitative immunostaining with CD31 (65, 66).