PHILADELPHIA, PA — In groundbreaking progress against one of the most lethal forms of brain cancer, an investigative team at Philadelphia’s Wistar Institute has unearthed a key tactic through which glioblastoma circumvents the body’s defenses. The findings, headed by assistant professor Filippo Veglia, Ph.D., were recently disclosed in Immunity, a scientific journal.
Revolutionizing our understanding of cancer’s self-preservation tactics, Dr. Veglia’s team found that glioblastoma—responsible for over half of all brain cancer cases—outsmarts the immune system, progressing unobstructed. This comes as a significant stride forward in the fight against a cancer that has a dire prognosis due to its aggressive growth and location.
The Wistar team’s focus was on monocyte-derived macrophages, a type of immune cell. As glioblastoma progresses, these macrophages increase in number within the tumor, superseding microglia, another type of immune cell. The increase in macrophages was seen as advantageous to the cancer’s evasion from immune response.
Using preclinical models, the team noticed that reducing the number of monocyte-derived macrophages within the tumor environment led to improved outcomes. This was a crucial breakthrough, as it affirmed the significant role these macrophages play in glioblastoma’s success.
The next step involved understanding how these immune cells, turned traitor by the cancer, undermine the immune system. Genetic sequencing of the macrophages revealed unusual gene expression patterns and highlighted the role of glucose metabolism. The cancer-allied macrophages, with amplified glucose metabolism and expressing a significant glucose transporter, GLUT1, were inhibiting the function of another type of immune cell, T cells, through the release of interleukin-10 (IL-10). IL-10 is produced to aid in cancer growth.
At the crux of the powerhouse macrophages lay a process called “histone lactylation,” a by-product of glucose metabolism, which essentially triggers the expression of IL-10.
Most significantly, Dr. Veglia’s team identified a possible combatant: an enzyme called PERK. Targeting PERK in preclinical models of glioblastoma impaired the macrophages’ immunosuppressive activity. When combined with immunotherapy, it also halted glioblastoma progression, offering potential long-term protection against tumor re-growth.
These findings offer new hope for glioblastoma treatment and shed light on the complex mechanisms within the body that cancer exploits to thrive. The ramifications of these insights could revolutionize our approach to cancer therapy, proving the significance of continued research in this vital area.
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