Immune Checkpoint Inhibitor (Ici) Therapy in Central Nervous System Cancers: State-Of-The-Art and Future Outlook Publisher



Keshavarz Sadegh R^{1, 2} ; Saleki K^{3, 4, 5, 6} ; Rezaei N^{4, 5, 7} Show Affiliations
Source: International Immunopharmacology Published:2025

Abstract

Invasive central nervous system (CNS) cancers are an area where the development of breakthrough therapies is urgently needed. For instance, conditions such as glioblastoma multiforme (GBM) are associated with poor clinical prognosis, with the majority of trials offering no improvement to marginally enhanced survival. Unleashing the potential of targeting the immune system in CNS cancers has gained attention in recent years. Inhibition of immune checkpoints such as CTLA-4, PD-1/PD-L1, TIM-3, and LAG-3 has been attempted in recent trials. While potentially offering a notable edge over other immunotherapies, multi-organ adverse events have been found with the administration of immune checkpoint inhibitors (ICIs). The present review captures the state-of-the-art evidence on ICI treatments in different CNS cancers. Also, we discuss the value of combinational therapies involving ICIs as well as next-generation therapeutics such as bispecific antibodies targeting PD-1/LAG-3/TIM-3 and CRISPR-Cas9-edited PD-1-knock-out checkpoint-resistant CAR T-cells. © 2025 Elsevier B.V.