Immunotherapy for glioblastoma: current state, challenges, and future perspectives

Cell Mol Immunol. 2024 Dec;21(12):1354-1375. doi: 10.1038/s41423-024-01226-x. Epub 2024 Oct 15.

Abstract

Glioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard of care offers minimal clinical benefit, and most GBM patients experience tumor recurrence after treatment. In recent years, significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers. However, the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles, GBM cell heterogeneity, and immunosuppressive tumor microenvironment. In this review, we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM. Furthermore, we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM, which will likely require combination therapies.

Keywords: Adoptive T-cell therapies; Glioblastoma; Immune checkpoint inhibitors (ICIs); Immunotherapy combination; Oncolytic viral therapies; Tumor vaccines.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / therapy
  • Glioblastoma* / immunology
  • Glioblastoma* / therapy
  • Humans
  • Immunotherapy* / methods
  • Tumor Microenvironment* / immunology