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PD-L1 in Extracellular Vesicles May Help Glioblastoma Evade Immunotherapies

The discovery suggests that the immune checkpoint can operate at a further distance from tumor cells than previously believed.

Mar 8, 2018
Jim Daley

WIKIMEDIA, JENSFLORIAN

Glioblastoma, a highly malignant and usually fatal form of brain cancer, is resistant to treatment in part because it can quickly develop resistance to both conventional and targeted therapies. A study reported this week (March 7) in Science Advances suggests that glioblastoma’s ability to disable immune checkpoints may be assisted by materials the tumor releases in extracellular vesicles.

Researchers at Brigham and Women’s Hospital found that the extracellular vesicles released by glioblastomas include programmed death ligand-1 (PD-L1), a protein that normally helps regulate T-cell activity. PD-L1 also appears on the surface of tumors, allowing them to remain hidden from circulating immune cells—a property that has made the protein an attractive target for checkpoint inhibitors, a type of immunotherapy.

See “How Cancers Evolve Drug Resistance

“This is the first time that anyone has observed that immune checkpoints can operate through extracellular vesicles and not just through the cell surface,” study coauthor Sean Lawler, a neurosurgeon at Brigham and Women’s Hospital, says in a statement. “This is a new concept, suggesting that these vesicles can work more distantly from the tumor cells.”

Glioblastoma was already known to produce extracellular vesicles, which contain molecular constituents such as DNA and RNA that can help tumors survive and grow. Lawler and his colleagues hypothesized that these vesicles—and the PD-L1 they carry—could play a significant role in immunosuppression. The researchers analyzed blood samples from patients with glioblastoma and compared them to samples from healthy people. They found that 14 out of 21 patients with glioblastoma had circulating extracellular vesicles that were enriched in PD-L1 DNA. They also observed that greater amounts of PD-L1 DNA corresponded to larger tumors.

According to the authors, this discovery may lead to a new way to detect glioblastoma in blood samples. However, they acknowledge in the press release that their results are based on a small sample and that subsequent studies are needed to determine whether PD-L1 can be a reliable biomarker.

See “Opinion: More Biomarkers Needed for Cancer Immunotherapy

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