“…Unfortunately, these combinations may cause severe immune-related adverse events, often leading to treatment discontinuation or hospitalization, and, sometimes, death. 6,7,8,9 The CD200 immune checkpoint results in suppression of the secretion of proinflammatory cytokines, including IL2 and IFNg, 10,11 and increases production of myeloid derived suppressor cells (MDSCs) 12 and T regulatory cells (Tregs), 12,13,14 resulting in compromised anti-tumor activity. Previously, we revealed the following mechanisms employed by the CD200 protein: (1) it is upregulated in GBM-associated endothelial cells, creating an immunological barrier around the tumor microenvironment; 10 and (2) it is shed from tumors 12,15 and interacts with the inhibitory CD200 receptor (CD200R1) on immune cells in the tumor microenvironment and within the draining lymph nodes.…”