CANCER, NEUROLOGY & NEUROSURGERY

Are Glioblastoma Cells Posing as Reproductive Cells to Evade Immune Response?

Sep. 22, 2021 - Eden McCleskey

Brain cancer cells may be able to successfully evade the body's immune response by masquerading as reproductive cells, according to a new finding under investigation at Houston Methodist.

The hospital's researchers have identified hundreds of glioblastoma tumors that express proteins associated with reproduction. When this occurs, patient outcomes are considerably worse, with death occurring on average twice as fast when compared to glioblastoma patients whose tumors don't express the proteins.

"We think this could potentially be a very important way in which tumors evade the immune system," says Dr. David Baskin, vice chair of the Houston Methodist Department of Neurosurgery. "People have been asking this question for a long time — why doesn't your immune system kill the cancer before it gets this far along? We are investigating this primarily in glioblastoma right now, but we believe it likely has implications for most cancer types."

Dr. Baskin will announce the finding at the American Academy of Neurological Surgery annual scientific meeting on Sept. 23. He told Leading Medicine the tactic employed by such tumors may represent an important potential Achilles heel for glioblastoma, the most lethal type of brain cancer.

Regulatory T-cells, or Tregs, typically help the body recognize its own tissues and arrest inflammatory immune responses to cells that are supposed to be there. In both men and women, Tregs recognize male and female reproductive hormones and proteins and suppress the antibody response towards them, even though they are foreign to the body prior to the onset of puberty. It's a free pass that helps promote the propagation of the species.

Cancer cells that express these sperm-specific and pregnancy-specific proteins may receive the same free pass that reproductive cells get, allowing them to replicate and grow into tumors without setting off the body's normally sophisticated alarm system. They do this by actually making male and female hormones and proteins associated with the reproductive process, which signals the Tregs to migrate in and shut down the body's immune response to the tumor. In this process, the immune system gets a fake signal that this is a reproductive cell and not a tumor.

If confirmed, the mimicry would represent a particularly savvy survival strategy for a cancer that's already so aggressive and fast-moving that no effective therapies or long-term cures exist. It is fatal virtually 100% of the time, with an average length of survival of 12-18 months.

If glioblastoma cells are indeed hijacking the privileged immunity that reproductive cells enjoy, there are established ways to interfere with that process.

"Typically, you do a study and you might have a single drug target to investigate that you hope might work," says Dr. Baskin, director of the Kenneth R. Peak Brain and Pituitary Treatment & Research Center at Houston Methodist. "The most exciting thing about this work is that, right off the bat, there are 10 or 11 existing off-the-shelf drugs that could do the job of telling your immune system not to look the other way anymore when it sees brain cancer cells. There are a number of vaccine strategies as well."

The investigation is ongoing, and the research team, which also includes Dr. Amanda Jensen and Martyn Sharpe, Ph.D., already has the first of several peer-reviewed publications under review. They expect it to be published later this year.