How biomarkers can personalize cancer immunotherapy
ASCO 2016 presenters share how combination therapies and biomarkers can better identify which tumors are likely to succumb to particular immunotherapies
With cancer immunotherapy’s successes have come growing pains and some unexpected challenges, experts said during a session entitled “What’s Next for Immunotherapy?” at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.
Research is under way to overcome these challenges. Combination therapies and biomarkers that can better identify which tumors are likely to succumb to particular immunotherapies, top the list.
“We’ve known for decades that cancer immunity matters,” noted session chair Vamsidhar Velcheti, MD, a professor of medicine at the Cleveland Clinic Lerner College of Medicine, during the June 6 presentation.
But it’s only been more recently that the molecular details of how tumors evade immune system attacks have yielded effective clinical treatment options, he said-most famously, immune checkpoint inhibitors such as agents that target programmed cell-death protein 1 (PD-1) and anti-PD-Ligand 1 (PD-L1).
Immune checkpoints are often likened to a car’s brakes: a safety mechanism that slows immune T-cell activation in order to prevent autoimmune attacks on the body’s own cells. Tumors can evolve to hit these brakes, suppressing T-cell attacks on cancer cells. Immune checkpoint blockade, like PD-1 inhibition, releases the immune system’s brakes.
“We’ve seen remarkable advances in immunotherapy, especially in the last year-an explosion of clinical trials for PD-1 immune checkpoint inhibitors,” Velcheti said.
New opportunities to address “moving targets”
PD-1 and PD-L1 inhibitors are now known to offer some patients durable responses against multiple cancer types, from melanoma and lung cancer to kidney, bladder, oropharyngeal and breast cancers.
But the “elephant in the room,” Velcheti acknowledged, is that not all patients benefit.
There are many potential reasons for that, including the fact that tumors represent a moving target. Even when targeting immune checkpoint blockade works initially, it will often eventually fail.
“Tumors evolve all the time,” Velcheti explained. “Immunogenic cancer clones are eradicated [by T cells] and there is selection for immune-evading cancer cells.”