Certain tasks in life must be performed in a specific order to work properly. You put your socks on before your shoes, and you wash your hands after you sneeze. To do otherwise would not yield the desired results.

New research suggests that this may also be the case in glioblastoma treatment. While immunotherapy has offered great benefit in treating several types of cancer, it has failed to show improvement in patients with glioblastoma. The devastating disease carries a median survival of under 15 months, and very few advances have been made in its treatment in years. New research offers fresh hope where it has long been missing.

Senior patient with headache talking to her doctor

This research, published in Nature Medicine, suggests that it may be the timing of the treatment in relation to surgical resection that determines the benefit of immunotherapy.

Patients given pembrolizumab, an immune checkpoint inhibitor, prior to surgical resection lived twice as long as those given the drug after surgery.

Pembrolizumab blocks a checkpoint that acts to stop immune cells from autoimmune attacks, but also from attacking tumor cells. So the inhibitor’s value is in blocking that checkpoint and allowing the immune cells to mount a response to the tumor. Pembrolizumab blocks the PD-1 checkpoint and is marketed under the trade name Keytruda.

The mechanism behind the difference in survival is believed to be connected with production of appropriate immune cells. When the tumor was resected first, fewer tumor-specific T cells were produced when immunotherapy was initiated.

But when the immunotherapy was initiated prior to surgery, more tumor-specific T cells were produced and remained after surgery, presumably because there was more antigen in the tumor to sensitize the immune system. This led to a more robust immune response from tumor-specific T-cells to the remaining tumor cells.

The study was a randomized trial of 35 patients, 16 of whom received pembrolizumab both before and after surgery, while 19 received the immunotherapy only after surgery. The study numbers were small, but the researchers point out the consistency of the results points to “an observable tissue-based and clinical treatment effect.”

These findings suggest that the presurgical administration of pembrolizumab enhances the antitumor immune response—both locally and systemically. Immunotherapy has proven effective in other malignancies such as melanoma and breast cancer, but its benefits had been previously eluded in glioblastoma treatment. Could it be that understanding the proper order of treatment is the key to unlocking its value?