May 19, 2025
Glioblastoma (GBM) is the most aggressive form of brain cancer. The tumor affects males more frequently and severely than females, and while treatment resistance and survival statistics are uniformly poor, females show significantly higher rates of both one-year and mean survival. David Page's lab is investigating the biological mechanisms behind these differences in hopes of uncovering new and targeted ways to intervene therapeutically. The researchers hypothesize that, because tumor development is regulated by the immune system, sex-associated immune interactions can underpin sex differences in cancer. With initial support from the Koch Institute Frontier Research Program in 2022, the Page lab has launched a study to explore the role of microglia—the brain’s primary resident immune cells—in shaping sex differences in glioblastoma biology.
Recent findings from the team suggest that microglia behave differently in the brains of males and females, creating environments that may either promote or restrain tumor development. This progress was recently highlighted in a preprint paper that highlights how sex-specific immune responses contribute to the differences in outcomes between males and females with GBM.
By comparing tumor-associated immune cells with normal microglia the team identified immune-associated inflammatory signatures in GBM and other, lower-grade brain tumors, that are associated with pro-tumor activity in males and anti-tumor activity in females. They demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this differential effect. These results implicate the tumor associated immune cells, specifically the sex chromosomes within the cells, as drivers of differences in GBM incidence and outcomes between males and females.
Current support for this research effort carries personal significance within the MIT and KI communities—the Samuel (1966) and Benjamin (2000) Krinsky Research Fund was established by Faith Krinsky following the deaths of her son Benjamin, an MIT student, from GBM in 1999 and husband, Samuel, from the same tumor in 2014. The Krinsky Fund is helping to support the Page lab’s follow-on GBM work, including the addition of research technician Hannah Scanlon, whose technical expertise and fresh perspectives will play a pivotal role in moving the project forward.
The Page lab’s work underscores the power of early philanthropic investment in addressing critical questions and challenges in cancer research. The Koch Institute Frontier Research Program empowers investigators and their collaborators to tackle high-risk, high-reward projects, and the Page lab’s work is expanding our understanding of how biological sex influences disease and treatment response, ultimately paving the way for better-tailored approaches to cancer care.