Decoding Brain Tumors: Why Some Resist Immunotherapy, According to Research

Brain Tumor Immunotherapy: UCLA Study Sheds Light on Brain Tumor Responses to Immunotherapy

Researchers from UCLA’s Jonsson Comprehensive Cancer Center have made a breakthrough in understanding why certain brain tumors respond to immunotherapy while others don’t. Their findings revolve around the presence and action of T cells, the soldiers of the immune system, and how these cells are activated to fight cancer.

Key Findings:

1. T Cell Activation in Metastatic Tumors: Tumors that have spread to the brain from other body parts exhibit a significant rise in both active and exhausted T cells post-immunotherapy. This suggests that T cells are successfully stimulated to counteract the cancer.

2. Glioblastoma’s Immunotherapy Resistance: Glioblastoma, a particularly aggressive brain cancer, doesn’t show this T cell activation. This is primarily because effective anti-tumor immune responses are ideally initiated in draining lymph nodes outside the brain, a process that’s ineffective in glioblastoma cases.

3. Comparison with Other Cancers: While immunotherapy hasn’t been fruitful against glioblastoma, it has shown promise in treating other cancers, like melanoma, which often spreads to the brain.

4. In-depth Analysis: The research team studied immune cells from patients treated with immune checkpoint blockade, a form of immunotherapy. Using single-cell RNA sequencing, they analyzed the genetic material from treated and untreated metastatic brain tumors and compared this to recurrent glioblastoma tumors. This helped ascertain the impact of immunotherapy on T cells.

5. T Cell Characteristics: The study found that in metastatic tumors, T cells exhibit specific features associated with combating tumors that enter the brain. This is likely due to better T cell activation that happens outside the brain.

6. T Cell Priming: T cells are usually primed in the lymph nodes, a process where dendritic cells inform T cells about the tumor, enhancing their tumor-fighting capabilities. This process isn’t as effective in glioblastoma treatment.

7. Exhausted T Cells and Survival Rates: A particular subset of exhausted T cells correlated with longer survival in patients with metastasized brain cancer.

In conclusion, Dr. Won Kim, one of the study’s authors, emphasized the significant difference in T cell response between metastatic tumors and glioblastomas post-immunotherapy. While metastatic tumors saw a substantial increase in T cells, glioblastomas showed a much milder rise. This research offers a promising foundation for refining immunotherapy treatments for different types of brain tumors.