Learning How Lung Cancer Co-opts the Immune System — and How to Fight Back
McGarry Houghton, Lung Cancer Immunologist
Sometimes Dr. McGarry Houghton wakes up the middle of the night thinking of neutrophils.
It’s probably safe to say most other people wouldn’t include these immune cells on a top-10 list of dream-worthy material.
But if they saw what Houghton sees, maybe they would.
The doctor and scientist at Fred Hutchinson Cancer Center is a leading expert in these poorly understood immune cells and their role in lung cancer, the deadliest cancer in the U.S. His research is demonstrating how neutrophils actually help cancers grow, rather than fight them. And his studies are paving the way for potential new therapies that could put an end to this betrayal, allowing the immune system to rally against cancers.
“I’m trying to figure these suckers out,” Houghton says with traces of his native Oklahoman drawl. “In all the time I’ve given to it I haven’t quite been able to put all the pieces together. But it’s accomplishable.”
Neutrophils and lung cancer
Your body makes legions of neutrophils to serve as front-line troops against infections, a role they play with gusto. When there’s a problem, they respond fast, their innards packed full of the cell-dissolving chemical weaponry they’re born with.
But they have a big weakness: They’re kind of dumb. “They’re not making sophisticated decisions about their environments — they react to them,” Houghton explained. Unlike other immune cells whose killing abilities are finely tuned to particular enemies and particular circumstances, neutrophils are more of the kill-first-ask-questions-later school. And as Houghton’s science has demonstrated, they can be manipulated by wily cancers and turned against you.
Houghton and colleagues published some of the seminal research demonstrating how tumors co-opt neutrophils for their own ends. Like the legendary Sirens of Greek mythology, cancer cells can emit an irresistible call to neutrophils by using the same signals that beckon these immune cells to fight infection. Then, once lured into your tumor, neutrophils switch sides and start working for the cancers, instead of for you.
This spells bad news: On average, the more neutrophils a patient has in their lung tumor, the shorter their survival time.
Exactly why the neutrophils go Benedict Arnold and what all they do in that role is the focus of intense research by Houghton’s team at Fred Hutch, where he leads the center’s lung cancer research group. Their next step, which is already underway, is developing targeted therapies that can prevent this turncoat behavior. The goal, Houghton says, is to “try and restore some order so that the immune system works better against cancer.”
“[Neutrophils are] not making sophisticated decisions about their environments — they react to them,” Houghton explained.
An accidental cancer biologist
Houghton, holder of the Satya and Rao Remala Family Endowed Chair, didn’t intend to become an expert in cancer biology. His medical training is in noncancerous lung diseases like emphysema, in which the lungs’ air sacs are damaged, typically by long-term cigarette smoking. He began his research career studying the neutrophils and other immunological links that connect tobacco smoke exposure and emphysema in mice.
Early on, a colleague asked for his help with a mouse study about smoking and lung cancer biology. Houghton didn’t know much about cancer at the time. So when he looked under the microscope at those mouse tumors, what popped out at him was not the cancer cells. It was the neutrophils. Lots and lots of neutrophils.
The cancer biologists who had been studying the same mice for years had never reported neutrophils in these tumors. They simply had glossed over the cells as background noise. But Houghton’s eyes were focused differently.
What were those cells doing there, he wondered?
His career, and his dreams, would never be the same.
— By Susan Keown, updated October 5, 2023
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