At Stanford Medicine, a team of immunologists has cracked a puzzle that has long stumped cancer researchers: how to reprogram the body's natural killer cells into warriors that can penetrate and destroy solid tumors, rather than simply circling helplessly in the bloodstream.
The breakthrough matters because most cell therapies have succeeded brilliantly against liquid tumors—cancers of the blood and lymphatic system—but have failed to infiltrate solid tumors, which are physically difficult to access and actively suppress any immune cells that get too close. Now, researchers led by Dr. John Sunwoo, the Edward C. and Amy H. Sewall Professor in the School of Medicine, have engineered tissue-resident natural killer cells that do something entirely different: they establish themselves inside tumors and kill cancer cells from within.
In animal testing, the researchers discovered that these specialized natural killer cells infiltrated solid tumors far more effectively than conventional natural killer cells. When combined with an antibody treatment that helps the cells target cancer cells, the therapy slowed tumor growth even further across a variety of tumor types in mice. The findings were published in Science Translational Medicine.
The team—led by co-authors Nina Horowitz, a former doctoral student in otolaryngology; Imran Mohammad, a postdoctoral fellow; and June Ho Shin, a senior scientist—found that the key lay in understanding how natural killer cells transform when they settle into tissue. Natural killer cells, named in the 1970s for their ability to immediately recognize and destroy abnormal cells, are unique among immune cells because they don't require prior exposure to a threat. Unlike B cells and T cells, they act as rapid responders, launching attacks on cancer and infected cells on sight.
The real innovation was recognizing that natural killer cells don't simply carry out the same functions everywhere. Some eventually migrate from the bloodstream and embed themselves in tissues like the skin, lungs, liver, and mucous membranes, where they adopt new identities and behaviors suited to their surroundings. Scientists had observed contradictory evidence about what these tissue-resident versions actually did—some appeared sluggish or even immunosuppressive, while others seemed to be highly efficient killers.
Sunwoo's insight was that these cells could shift behavior depending on signals in their environment. For pregnancy, tissue-resident natural killer cells intentionally suppress immune responses to protect the developing fetus. But for cancer, researchers could engineer them to activate their killer instincts instead.
Perhaps most exciting for patients is that natural killer cells don't trigger an immune rejection when transferred from one person to another. Unlike most personalized immunotherapies, which must be manufactured individually from each patient's own cells, supercharged natural killer cells could be mass-produced, frozen, and given to any patient who needs them. "It would be almost an off-the-shelf drug," Sunwoo said. "It could make cell therapy much more accessible to a wider variety of patients."
The path from mouse models to human trials remains ahead, but Stanford's work points toward a future where cell therapy becomes democratized—no longer an expensive, individualized treatment reserved for a few, but a standardized medicine that could help many.