Immune checkpoint inhibitors show promise in brain tumors, questions remain

The promise of immune checkpoint inhibitors in systemic cancers such as melanoma, non-small-cell lung cancer and breast cancer has prompted researchers to start examining the potential for these immunotherapies in the management of primary and metastatic brain tumors, according to Peter A. Forsyth, MD, FACP, MA, of the H. Lee Moffitt Cancer Center & Research Institute at the University of Southern Florida.

“It’s early … but [we know that] mostly the immune checkpoint inhibitors, for example, are releasing the brakes on activating T cells … that hopefully allow the immune system to both recognize and attack the tumors and presumably leave the normal tissue alone,” Forsyth told HemOnc Today.

Peter A. Forsyth

How this relates to the brain – both for primary gliomas or metastatic tumors, such as melanotic tumors, and hematologic tumors, including primary CNS lymphoma or lymphoma that metastasizes to the brain – is unclear at this point, according to Forsyth.

There have been a number of responses that demonstrate long-term stability of disease that have been impressive in some of the metastatic tumors, Forsyth said.

The use of anti-PD-1s and anti-CTLA-4s and similar treatments have produced comparable response rates for brain metastasis as has been seen in systematic cancers, according to Forsyth.

“Some of the early published studies and evolving studies are showing that the response rates are about the same in the brain as they are with systemic disease,” he said.

However, Forsyth acknowledges there are some challenges in applying immune checkpoint inhibitors in the treatment of brain tumors.

One challenge Forsyth highlights is the interplay of T cells and the dendritic cells in CNS.

“It might be necessary to turn on an initial immunologic response to a primary glioma cell … so there will be a target that can at least be recognized by the activated T cell,” he said.

Strategies to accomplish this may include radiation that might unleash new antigens and possibly uncover antigens that have previously been silent to the immune system, according to Forsyth. Additionally, other approaches could include injecting attenuated or live viruses, bacteria or toll-like receptor agonists that would turn on antigen presentation and perhaps make the immune therapy more effective, he said.

“It’s an extremely exciting time and filled with promise, but what the particular immunologic approaches would be and how these should be combined with other therapy is really unclear right now,” he said. “There’s many years of work ahead of us to uncover whether this is going to be useful or not.” – by Ryan McDonald

Disclosure: Forsyth reports no relevant financial disclosures.