Fig. 1.

ICB increases GBM vascular leakage and induces brain edema. MR T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) images obtained from a recurrent GBM patient (A) before and (B) after 4 mo of anti-PD-L1 (MEDI4763; NCT02336165) treatment show increased edema after ICB treatment. In addition to ICB-induced inflammation, this change may be due in part to underlying tumor activity or growth. (C) In mice, anti-PD1 antibody (aPD1) treatment increases edema in GL261 tumors compared to IgG control [as measured by wet-dry weight (i.e., water content) evaluation of tumor tissue; n = 5]. Multiphoton visualization of the brain vasculature via injected tetramethylrhodamine (TAMRA) labeled albumin (red) imaged through transparent cranial windows in mice bearing GFP+ GL261 GBM (green) shows that compared to IgG controls (D) there is increased extravasation in anti-PD1-treated tumors after the third consecutive dose (E). (F) Quantification shows that more albumin in anti-PD1-treated mice has leaked outside of the tumor blood vessels (n = 3). (Bar plots: mean ± SEM; Student’s unpaired t test; *P < 0.05; ***P < 0.001.)