To reveal the difficulties imposed upon ICB treatment specifically by the intracranial (IC) TME, we compared the efficacy of a combination therapy consisting of ICB antibodies against programmed cell death protein 1 (PD1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) in subcutaneous (SQ) and IC GBM models in WT mice. This evidence concerns the gene PDCD1 and glioblastoma.