Publication Summary:

Immune checkpoint inhibitor therapy is offering new hope for many types of cancer. It works by deactivating a cancer cell’s ability to cloak itself against our immune system’s defenses. Normally, checkpoints keep our immune system from over-reacting to healthy cells in the body. They occur as proteins on the surface of a cell that bind to a protein on our immune system’s T cells, turning off their killer response.  But some cancer cells mimic these proteins on their surfaces, allowing them to evade destruction.

To date, checkpoint inhibitor therapy has not shown much success against pediatric cancers. But a new study from researchers at the Dana Farber Institute and Boston Children’s Hospital may offer hope for patients with ATRT.

To date, the only common genetic feature identified in ATRT has been the inactivation of a gene called SMARCB1, which provides instructions for making a protein called INI1, When production of these proteins goes awry in these INI1-negative tumors, the door is opened to cancer-causing mutations like checkpoint proteins.

Investigators involved in this study noted that patients with tumors lacking the INI1 protein were achieving some response to targeted therapies. They checked available INI1-negative tumor samples for the presence of cancer-killing T cells and looked at levels of PD-L1, a protein that helps cancer cells to evade these killer T cells. Their results showed more than half of the tumor specimens contained the killer T cells – and almost half were positive for the immune system-evading protein. This indicates potential for response to checkpoint inhibitor drugs, and a clinical trial based on this study's results is already underway.