Clinical investigations of immunotherapy for human primary brain tumors

Human primary brain cancer is one of the most lethal and clinically challenging malignancies. The failure of conventional therapies to alleviate its poor outcome has prompted efforts to find innovative treatments. Recent breakthroughs in immunotherapy across a variety of solid tumors have set immune-based therapeutics as a pillar for brain cancer treatment. However, the unique features of brain malignancies including intratumoral heterogeneity, immunosuppressive microenvironment, and impervious blood-brain barrier, thwart the success of immunotherapeutic approaches. Yet, seminal findings regarding tumor-driven enrichment of specific immune cells granted the field novel insights to harness the immune cells to fight cancer. This review discusses the anatomical, microenvironmental, and immunobiological features of the human brain and presents an overview of immunotherapies tested for primary brain cancer patients with a special emphasis on registered phase 2, 3, and combinatorial clinical trials. Immune checkpoint inhibitors, immune cell-based therapies, cancer vaccines, oncolytic viral therapy, and combination therapies are investigated in clinical settings for the treatment of human brain tumors. Despite their occasional adverse effects, immune-targeted therapies provide a promising opportunity for primary brain cancer patients to enhance survival and improve prognosis