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Researchers Seek to Understand Why Lungs Are Susceptible To Cancer

Lung Cancer Awareness Month - Mesothelioma

The body has a cadre of defense mechanisms that work together to fight off illness and diseases. When they fail, however, a person can be left fighting a deadly disease like mesothelioma. Now, researchers believe that the same defense meant to prevent people from having a reaction to breathing in daily environmental exposures could be the same mechanism that allows cancer cells to spread and grow in the lungs.

According to an Aug. 25 press release from the Ohio State University Comprehensive Cancer Center, researchers report that the oxygen breathed in can suppress immune responses to cancer. They found that oxygen-sensing proteins, or PHD cells, limit inflammation by T-cells, the cells in the immune system that kill bacteria and cancer. In the “highly oxygenated lung microenvironment” the PHDs limit the T-cell functions, thus, setting the lung up as a “fertile ground for metastasis.”

“The same ‘normal’ mechanisms put in place to suppress immune responses against harmless material taken into the body during the act of breathing can also suppress immune responses to the colonizing cancer cells that lead to metastatic tumors in the lungs,” said David Clever, PhD, first author of the manuscript and a current medical student at Ohio State. “This creates an immunologically favorable niche – meaning the environment is prime for cancer cells to slip through the immune system’s defenses, thrive and grow in the lungs.”

The American Cancer Society reports that it is cancer metastasis, and not the original cancer diagnosis itself, that is the cause of nearly all cancer deaths. In fact, 90 percent of all cancer deaths are due to metastasis. Lung cancer and mesothelioma can spread to other organs of the body, including spreading to the other lung.

Mesothelioma, an unusual form of cancer caused by breathing in asbestos fibers, can take decades to show symptoms. Mesothelioma treatment follows a similar treatment protocol to lung cancer, so each new discovery related to lung cancer brings hope to the patient community.

The Ohio State team found that by blocking the PHD proteins, they could enhance T-cell responses against cancer and limit metastasis to the lung. Through testing the theory in mice using adoptive cell transfer immunotherapy, or manipulation and re-injection of T-cells, the researchers were hopeful their findings could lead to new therapies.

“Although our finding is in mice, we are eager to test whether disruption of the oxygen sensing machinery in T cells — with drugs, genetics, or regulation of environmental oxygen — will enhance the efficacy of T-cell mediated immune therapies for cancer in humans.”

2,500 to 3,000 people are diagnosed with mesothelioma each year in the U.S. There is no cure for the cancer, however, immunotherapy treatments, available to limited patients, have shown success in extending survival in mesothelioma patients.

The study can be found in the Aug. 25 issue of the journal Cell.

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Last Modified: November 21, 2018

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