A landmark study headed by researchers at Yale School of Medicine and at Fred Hutchinson Cancer Center has revealed that autoantibodies (AAbs)—immune proteins traditionally associated with autoimmune disease—may profoundly influence how cancer patients respond to checkpoint immunotherapy (CPI).
Results from the research, involving humans and mice, could represent a potential breakthrough in solving one of modern-day oncology’s most frustrating mysteries, which is why checkpoint inhibitors work for some patients but not others. The findings could indicate how it may be possible to extend treatment benefits to more people, and suggest that autoantibodies could help reveal cancer’s weak spots and point to new therapeutic targets.
“Our analysis shows that certain naturally occurring autoantibodies can tilt the odds dramatically toward shrinking tumors,” said Aaron Ring, MD, PhD, an associate professor at Fred Hutch Cancer Center. “We saw some cases where autoantibodies boosted a patient’s likelihood of responding to checkpoint blockade by as much as five- to ten-fold.”
Ring is senior author of the team’s published paper in Nature, titled “Humoral determinants of checkpoint immunotherapy,” in which the researchers say their findings “… highlight therapeutically actional pathways that can be exploited to augment immunotherapy.”
Autoantibodies are immune system proteins that recognize the body’s own tissues. They are most associated with their harmful role in driving autoimmune diseases like lupus or rheumatoid arthritis. However, emerging evidence indicates that in some cases, autoantibodies can surprisingly exert health benefits. “Beyond their classical role in driving autoimmunity, self-reactive AAbs have been established to exert profound biological influences on health and disease,” the authors wrote. However, they noted, “… few studies have comprehensively explored the breadth of AAb reactivities at a proteome scale (the ‘AAb reactome’) in patients with cancer.”
“For years, autoantibodies were viewed mainly as bad actors in autoimmune disease, but we’re discovering they can also act as potent, built-in therapeutics,” said Ring, who holds the Anderson Family Endowed Chair for Immunotherapy at Fred Hutch. “My lab is mapping this hidden pharmacology so we can turn these natural molecules into new treatments for cancer and other illnesses.”
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