The microenvironment of glioblastoma: in pursuit of universal multimodal immunotherapy

Glioblastoma (GBM) is a highly malignant primary brain tumor known for its heterogeneity, infiltrative growth, and poor prognosis. Standard treatment includes surgery, radiation, and chemotherapy. Although the therapeutic options remain limited, immunotherapy provides new hope for treating GBM that has relapsed following standard therapies by boosting the immune system to inhibit tumor growth. The tumor immune microenvironment (TME) plays crucial roles in GBM progression and immunotherapy resistance. Since activated immune cells can penetrate far-off and impenetrable tumor cells, immunotherapy is a viable alternative. Immunotherapy has improved patient outcomes for a number of cancers and may offer GBM patients new, more efficient treatment options. To address both the innate and acquired immune responses in GBM patients, researchers are currently investigating a variety of immunotherapeutic approaches. Immune checkpoint mechanisms are emerging as promising targets. Furthermore, CAR-T-cell therapy offers new hope for enhancing treatment efficacy. Understanding the interplay between the TME, immune checkpoints, and therapeutic modalities is crucial for developing new standards of treatment. Thus, this review discusses recent advancements, challenges, and future directions in immunotherapy for patients with glioblastoma.