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AANS Neurosurgeon | Volume 27, Number 4, 2018

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Study finds macrophages’ pathway to nurture PTEN-deficient glioblastoma

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A common genetic deficiency empowers glioblastoma to broadcast a molecular message to the wrong type of immune cell, summoning macrophages that protect and nurture the brain tumor instead of attacking it, researchers at The University of Texas MD Anderson Cancer Center report.

The team’s work in mouse models of glioblastoma that lack functional cancer-suppressor gene PTEN points to new potential targets for treating the most common and lethal brain tumor, said senior author Ronald DePinho, MD, professor of Cancer Biology and past president of MD Anderson.

About a third of all glioblastomas are PTEN-deficient. Median survival for glioblastoma is about 12 to 15 months, and only 5 percent of patients survive for five years.

“We’ve identified a symbiotic circuit that is activated in PTEN-deficient glioblastoma which creates a mutually supportive relationship between the cancer cell and macrophages that come into the tumor microenvironment and provide growth factor support for the tumor,” DePinho said.

Macrophages engulf and digest microbes, cellular debris and tumor cells as part of an immune response, and they secrete cytokines that affect other cells. They are bipolar. In their M1 form, they actively assist immune response and inhibit tumor growth. In M2, they are in repair mode, helping post-immune recovery, which can also promote cancer growth and progression.

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