FIGURE 1.

Routes of CNS-based tumor antigen drainage to regional lymph nodes. Tumor-derived antigens can reach draining cervical lymph nodes in several ways. Antigen that gains access to the CSF either by direct extension of the tumor, breakdown of the BBB, cellular trafficking by APC, or through glymphatic exchange can enter the lymphatic system by traversing the cribiform plate into the nasal mucosa (1) or through meningeal lymphatics of the dura (3). Alternatively, acellular antigen can enter the wall of intraparenchymal capillaries and arteries to migrate retrograde toward local lymph nodes (2). BBB, blood–brain barrier; CSF, cerebrospinal fluid; GBM, glioblastoma; ISF, interstitial fluid. Adapted from Engelhardtet al.⁴