Extrinsic factors associated with the response to immunotherapy in glioblastoma

Glioblastoma (GBM) is a heterogeneous and lethal brain tumor. Despite the success of immune checkpoint inhibitors against various malignancies, GBM remains largely refractory to treatment. The immune microenvironment of GBM is highly immunosuppressive, which poses a major hurdle for the success of immunotherapy. Obviously, except for the GBM cells itself, there are also extrinsic reasons for the lack of efficacy of immunotherapy. Accumulated evidence indicates that factors other than GBM cells determine the efficacy of immunotherapy. In this review, we first described the unique immune microenvironment of the brain, which must be considered when using immunotherapy in patients with GBM. Second, we also described the mechanisms by which different immune and non-immune cells in the GBM microenvironment affect the efficacy of immunotherapy. Furthermore, the impact of standard therapies on the response to immunotherapy was delineated. Finally, we briefly discussed strategies for resolving these problems and improving the efficacy of immunotherapy.