Scientists identify clues to making immunotherapy more effective against glioblastoma

Two new studies by UCLA Health researchers shed light on how to more effectively activate the immune system against glioblastoma, the most aggressive form of brain cancer.

In one study published in Nature Communications, researchers found that combining two immune checkpoint inhibitors, nivolumab and ipilimumab, before surgery led to a stronger immune response compared to using nivolumab alone. Patients receiving the combination therapy lived longer, with median survival of 13.5 months compared to 9 months for those treated with nivolumab alone.

About 15% of combination therapy patients became long-term survivors, while none of those on nivolumab alone did. The combination also triggered greater immune activity within tumors, including higher numbers of cancer-fighting T cells and expression of interferon-related immune genes. T-cell density within tumors emerged as an independent predictor of survival and a potential biomarker to identify patients likely to benefit from such therapies.

A second study in Cancer Research introduced a more accurate preclinical model of glioblastoma that better replicates the genetic, biological and immune aspects of human disease. Using a technology called MADR, the model introduces patient-relevant genetic changes into developing brain cells. This includes common genetic alterations like EGFRvIII and loss of tumor suppressor genes PTEN and CDKN2A.

The model provides a more faithful representation of why glioblastoma often resists immunotherapy, allowing researchers to study resistance mechanisms and test new therapies. The studies together offer new insights into effective immune responses against glioblastoma and guide the development of next-generation treatments to improve outcomes for patients.