Immune Cells Play Role in Dictating Lung Cancer Susceptibility

Lung cancer is the most common cause of cancer death not only in the United States, but also in the world. According to the lung cancer statistics, more people in the United States die from lung cancer than any other type of cancer. A novel study highlights the key immune cell that plays a vital role in lung cancer susceptibility.

This research was conducted at Washington University School of Medicine in St. Louis. The study on the mice revealed that the genetic diversity in natural killer cells, which typically seek out and destroy tumor cells, contribute to whether or not the animals develop lung cancer.

 "Overall, humans are genetically very similar but their immune systems are incredibly diverse," explains senior author Alexander Krupnick, MD, a thoracic surgeon at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "Our findings add to the growing body of evidence suggesting that innate differences in immunity may determine not only a person's susceptibility to colds but also to lung cancer."

Based on the findings in mice, Krupnick says, "We now are studying whether humans have a similar genetic diversity in their natural killer cells. As part of a new clinical study, we're analyzing the blood of heavy smokers with and without lung cancer and never-smokers with and without lung cancer to look for differences."

"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," says Krupnick, associate professor of surgery. "And, by comparison, do patients who have never smoked but develop lung cancer have weak natural killer cells?"

In order to conduct the study on mice, the researchers evaluated three groups of mice with varying susceptibilities to lung tumors. The mice were exposed to carcinogen, which triggers lung cancer. On being exposed to carcinogen one group readily developed the disease while another showed little evidence of the tumors. A third group experienced moderate tumor growth.

On reducing the natural killer's cell from the mice using an antibody, those that had been resistant to lung cancer developed large, aggressive tumors.

For the mice that were susceptible to lung cancer, the scientist noticed that by altering the immune system with a bone marrow transplant it could significantly block the development of lung cancer. The study highlights that the natural killer cells, not other types of immune cells like T cells or inflammatory cells, are responsible for this phenomenon.

In other types of cancers, including those of the breast, colon and prostate, T cells are capable of destroying tumor cells. But in lung cancer, scientists suspect that T cells become inactivated, which may give natural killer cells a more prominent role.

They simultaneously observed the genetic diversity of the natural killer cells in the mice to a region of chromosome 6, which includes numerous genes that influence the effectiveness of these cells.

"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?' The answer will determine our next steps." says Krupnick. 

 The details of this study were produced in the September Cancer Research.