Key immune cell may play role in lung cancer susceptibility

September 21, 2012 by Caroline Arbanas

(Medical Xpress)—Why do many heavy smokers evade lung cancer while others who have never lit up die of the disease? The question has vexed scientists for decades.

Now, new research at Washington University School of Medicine in St. Louis suggests a key immune cell may play a role in lung cancer susceptibility. Working in mice, they found evidence that the in , which typically seek out and destroy tumor cells, contributes to whether or not the animals develop lung cancer.

The research is published in September in .

"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 he and his colleagues now are studying whether humans have a similar genetic diversity in their cells. As part of a new clinical study, they'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 who don't get lung cancer have natural killer cells that are somehow better at destroying newly developing ," says Krupnick, associate professor of surgery. "And, by comparison, do patients who have never smoked but develop lung cancer have weak natural killer cells?"

For the mouse study, the scientists evaluated three groups of mice with varying susceptibilities to . After the mice were exposed to a carcinogen that causes lung cancer, one group readily developed the disease while another showed little evidence of the tumors. A third group experienced moderate tumor growth.

When the researchers depleted natural killers cells from the mice using an antibody, those that had been resistant to lung cancer developed large, aggressive tumors.

Further, in mice susceptible to lung cancer, the scientists showed that manipulating the immune system with a bone marrow transplant could significantly block the development of lung cancer. Their studies indicate that natural killer cells, not other types of 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 . But in lung cancer, scientists suspect that T cells become inactivated, which may give natural killer cells a more prominent role.

The researchers also traced 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.

Moving forward, Krupnick and his team want to learn whether natural killer cells influence lung cancer susceptibility in people. "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 ?' The answer will determine our next steps."

Explore further: Latest research confirms genetic susceptibility to lung cancer

More information: Kreisel D, Gelman AE, Higashikubo R, Lin X, Vikis HG, White JM, Toth KA, Deshpande C, Carreno BM, You M, Taffner SM, Yokoyama WM, Bui JD, Schreiber RD, Krupnick AS. Strain-specific variation in murine natural killer gene complex contributes to differences in immunosurveillance for urethane-induced lung cancer. Cancer Research. September 2012.

Related Stories

Latest research confirms genetic susceptibility to lung cancer

April 15, 2012
Previous research has shown that Asian patients with lung cancer are more likely to harbor epidermal growth factor receptor (EGFR) mutations. Furthermore, Asian patients with lung cancer are more likely to be non-smokers ...

Protein boosts lung cancer in smokers, non-smokers; Potential anti-oncogenic target

July 19, 2011
Lung cancer is strongly correlated with smoking, and most lung cancer patients are current or former smokers. But it is not rare in nonsmokers. Now, a team of researchers from the H. Lee Moffitt Cancer Center and Research ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.