Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma

Bryan Gardam; Tessa Gargett; Michael P Brown; Lisa M Ebert

doi:10.3389/fimmu.2023.1261257

Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma

Front Immunol. 2023 Oct 20:14:1261257. doi: 10.3389/fimmu.2023.1261257. eCollection 2023.

Authors

Bryan Gardam^{1

2}, Tessa Gargett^{1

2

3}, Michael P Brown^{1

2

3}, Lisa M Ebert^{1

2

3}

Affiliations

¹ Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
² Translational Oncology Laboratory, Centre for Cancer Biology, University of South Australia and South Australia (SA) Pathology, Adelaide, SA, Australia.
³ Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.

Abstract

Glioblastoma is an aggressive primary brain tumor that has seen few advances in treatments for over 20 years. In response to this desperate clinical need, multiple immunotherapy strategies are under development, including CAR-T cells, immune checkpoint inhibitors, oncolytic viruses and dendritic cell vaccines, although these approaches are yet to yield significant clinical benefit. Potential reasons for the lack of success so far include the immunosuppressive tumor microenvironment, the blood-brain barrier, and systemic changes to the immune system driven by both the tumor and its treatment. Furthermore, while T cells are essential effector cells for tumor control, dendritic cells play an equally important role in T cell activation, and emerging evidence suggests the dendritic cell compartment may be deeply compromised in glioblastoma patients. In this review, we describe the immunotherapy approaches currently under development for glioblastoma and the challenges faced, with a particular emphasis on the critical role of the dendritic cell-T cell axis. We suggest a number of strategies that could be used to boost dendritic cell number and function and propose that the use of these in combination with T cell-targeting strategies could lead to successful tumor control.

Keywords: CAR-T cells; T cells; brain tumor; cancer; combination therapies; dendritic cells; glioblastoma; immunotherapies.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Dendritic Cells
Glioblastoma*
Humans
Immunotherapy
Oncolytic Viruses*
T-Lymphocytes
Tumor Microenvironment

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grant 2020344 awarded through the 2022 Priority-driven Collaborative Cancer Research Scheme and co-funded by Cancer Australia and The Kids’ Cancer Project; additional funding was provided by the Neurosurgical Research Foundation, Tour de Cure, the Ray & Shirl Norman Cancer Research Trust, the Mark Hughes Foundation, and the Health Services Charitable Gifts Board Adelaide.