Brainstem tumors in children are a significant health concern, particularly because they are difficult to treat and often lead to poor outcomes. Understanding these tumors’ genetic and molecular characteristics can provide valuable information that may lead to better treatment strategies. By examining specific markers in the tumor environment, researchers are beginning to uncover how these factors influence survival outcomes in young patients, offering hope for more effective therapies in the future.

Researchers from Oncotelic Therapeutics, led by Dr. Sanjive Qazi along with Dr. Zahra Talebi, and Dr. Vuong Trieu, have unveiled a critical correlation between mRNA levels of specific biomarkers and overall survival in pediatric diffuse midline glioma (DMG) patients. Their study, published in Biomedicines, provides pivotal insights into the impact of the tumor microenvironment (TME) on disease prognosis.

The team explored the expression profiles of transforming growth factor beta 2 (TGFB2) and interferon-gamma receptor 2 (IFNGR2) in the brainstem TME of pediatric DMG patients. This research aimed to identify potential biomarkers that could predict survival outcomes and inform therapeutic strategies. The study analyzed mRNA levels in tumor samples and compared them with normal brainstem tissue, revealing significant findings.

“High levels of TGFB2 and low levels of IFNGR2 in the tumor microenvironment were associated with significantly worse overall survival outcomes,” said Dr. Qazi. “This suggests that the TME’s immune suppression and tumor progression mechanisms play a crucial role in patient prognosis.”

The researchers discovered that pediatric brainstem DMG tumors exhibited elevated TGFB2 mRNA levels and decreased expression of antigen-presenting cell (APC) markers such as CD14, CD163, and ITGAX/CD11c compared to normal brainstem tissue. These markers are essential for the immune system’s ability to recognize and attack tumor cells. The findings indicate that high TGFB2 levels contribute to an immunologically “cold” tumor environment, hindering the body’s anti-tumor response.

In their analysis, the team employed multivariate Cox proportional hazards modeling to evaluate the prognostic significance of TGFB2 and IFNGR2 expression levels. They found that high TGFB2 expression strongly predicted poor overall survival, independent of other factors such as patient age and the interaction between TGFB2 and IFNGR2 levels.

“The data suggest that targeting TGFB2 in combination with strategies to enhance IFNGR2 signaling could potentially improve survival outcomes for pediatric DMG patients,” noted Dr. Qazi. “This dual approach might help to lift the immunosuppressive environment and stimulate a more effective anti-tumor immune response.”

The study underscores the complexity of the brainstem TME in pediatric DMG. It highlights the need for therapies that not only target the tumor cells but also modulate the immune environment to enhance the body’s natural defenses against cancer. The researchers emphasize that future treatments could involve inhibiting TGFB2 production while simultaneously activating immune cells through IFN-γ stimulation.

“Our most important conclusion is that the TME’s role in DMG progression is pivotal,” said Dr. Qazi. “Understanding these interactions at the molecular level opens new avenues for developing targeted therapies that can improve patient outcomes.”

This research by Dr. Qazi, Dr. Talebi, and Dr. Trieu marks a significant step towards more effective treatment strategies for pediatric DMG, a highly aggressive and challenging cancer. By identifying and targeting specific molecular pathways in the TME, scientists hope to develop therapies that can significantly extend the lives of young patients battling this devastating disease.

Journal Reference

Qazi, S., Talebi, Z., & Trieu, V. (2024). Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients. Biomedicines, 12(1), 191.  DOI: https://doi.org/10.3390/biomedicines12010191