Key immune cell may determine lung cancer susceptibility

New research at the Washington University School of Medicine has found that genetics may play a previously misunderstood role in individuals’ contraction of lung cancer.

In a study published in September’s “Cancer Research” journal, scientists found that genetics—specifically, the “natural killer cell,” a key component of the immune system— may be the defining factor in susceptibility to lung cancer, explaining why people who smoke the same amount can have vastly different physical responses.

“We want to know whether heavy smokers who don’t get lung cancer have natural killer cells that are somehow better at destroying newly developing lung cancer cells,” said senior author Alexander Krupnick, MD, a thoracic surgeon at the Siteman Cancer Center at Barnes-Jewish Hospital and the Washington University School of Medicine. “And, by comparison, do patients who have never smoked but develop lung cancer have weak natural killer cells?”

In the study, University researchers examined three groups of mice with varying susceptibilities to lung cancer, exposing each group to carcinogens that cause lung cancer. One group quickly developed the disease, another group developed aggressive tumors and the third group developed only moderate tumor growth.

However, when researchers deactivated the natural killing cells, the mice that were originally resistant to lung cancer showed the same reaction as the other groups, developing large and aggressive tumors.

In a study the researchers had previously conducted, a bone marrow transplant was able to block the development of lung cancer. A bone marrow transplant is used to replace diseased or damaged bone marrow, which produces stem cells that can become the necessary immune cells.

With these findings, researchers concluded that natural killer cells determine genetic susceptibility to lung cancer. In other cancers, T-cells are generally responsible for tumor growth; but with lung cancer, scientists believe T-cells are for some reason deactivated. That makes the natural killer cells even more important to hindering or destroying nascent tumors.

In the mice studies, researchers identified a diversity of natural killer cells from a region in chromosome 6, where many genes that influence these cells are located.

The conclusions from this new clinical study have many implications for the prevention of lung cancer, perhaps even at the genetic level, and for individuals from families of smokers or those with lung cancer.  

However, the study and its findings have much left to explore. Krupnick and his colleagues have begun looking to see if the findings are relatable to contraction of cancer in humans.

“We need to identify those patients who are resistant to lung cancer and ask, ‘What is unique about their natural killer cells—are they more potent or do they produce more of them than people with lung cancer?’” Krupnick said. “The answer will determine our next steps.”

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