July 2026

NEUROSCIENCES

IMMUNOTHERAPY STRATEGY SHOWS PROMISE FOR GLIOBLASTOMA

A new immunotherapy strategy has shown promise as a glioblastoma treatment by targeting the tumor and tumor-supportive macrophages simultaneously, according to a new study published in Nature.

Targeting Tumors — and the Noncancerous Cells Supporting Them
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“Glioblastoma is notable for having a high frequency of tumor-supportive macrophages that promote the tumor vasculature, facilitate brain invasion, mediate drug resistance and suppress the immune response against the glioma,” says Amy Heimberger, MD, PhD, a co-author of the study.  

The investigators were led by Sheila Singh, MD, PhD, joint head of the School of Cancer and Pharmaceutical Sciences and head of the Comprehensive Cancer Center at King’s College London. Using a multi-omics discovery platform, they identified a protein called GPNMB on both glioblastoma tumor cells and the immunosuppressive macrophages supporting them. 

After immune cell analysis, the investigators found that the macrophages expressing GPNMB are among the most immunosuppressive. In lab and animal models, CAR-T cells engineered to target GPNMB showed that they were able to attack both tumor cells and the tumor-supporting macrophages. Investigators then tested the therapy in human tumors grafted in mice and fully immune-competent mouse models. Across these, the therapy showed strong anti-tumor activity. 

Elimination of Immunosuppressive Macrophages May ‘Reset’ Tumor Environment

“There have been prior attempts at trying to reprogram tumor-supportive macrophages and those failed in clinical trials because the macrophages can shift between functional states,” Dr. Heimberger explains. The new approach, she adds, may be more effective because it removes those cells altogether rather than trying to change their behavior.

“Rather than viewing glioblastoma purely as a collection of neoplastic cells, we need to think of it as an ecosystem in which tumor cells and tumor-supportive macrophages work together. In this framework, any approach that targets only the tumor or only the macrophages is incomplete,” Dr. Singh says.

Moving forward, investigators are exploring how best to deliver CAR-T cells to the brain safely and effectively. 

The study was supported by the Terry Fox Research Institute Program Project Grant (1065), a translational grant from Brain Canada and the Canadian Research Society, as well as funding from the Canadian Institutes for Health Research, the Brain Tumor Foundation of Canada and Brain Cancer Canada. Additional funding came from NIH grants R01 CA120813, R01 NS120547 and P50 CA221747. 
Amy Heimberger, MD, PhD, the Jean Malnati Miller Professor of Brain Tumor Research and vice chair for research in the Department of Neurological Surgery, was a co-author of the study.

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