The blood supply of a tumor often does not match the pace of the
cancer’s growth, which leads to areas that are ischemic, or oxygen
deprived, explained Edwin Jackson, Ph.D., professor of pharmacology and
chemical biology, Pitt School of Medicine, and a co-author of a paper published online today in Science Translational Medicine.
That causes the tumor cells to make adenosine, a molecule that not only
promotes blood flow, but also binds to a receptor on killer T-cells and
essentially puts them to sleep. In effect, adenosine acts as a shield
against immune system cells that would otherwise attack the cancer.
“We realized if we could find a way to block the increase in
adenosine, we might be able to help the immune system respond to the
tumor to make anti-cancer therapies more effective,” Dr. Jackson said.
“This study shows that simply breathing more oxygen can accomplish that
aim, which could lead to an amazing breakthrough in cancer treatment.”
The study team, led by Michail Sitkovsky, Ph.D., director of the New England Inflammation and Tissue Protection Institute at Northeastern University,
exposed mice with lung tumors to respiratory hyperoxia at levels of 40
to 60 percent oxygen, comparable to what patients might receive in the
hospital. Another group of mice breathed air, which is approximately 21
percent oxygen. Tumors in mice that received supplemental oxygen shrank –
some regressed completely – and the animals were more likely to survive
than those on room air.
“Supplemental oxygen prevented the tumor from making extra
adenosine, so the immune cells could do their job and attack the cancer
cells,” Dr. Sitkovsky explained. “But if anti-tumor immune cells aren’t
present, oxygen has no effect. We hope we will soon see clinical trials
of respiratory hyperoxia in combination with immunotherapies to see
whether it can help cancer patients.”
He noted also the effects might be stronger in combination with an
agent that he calls “super-caffeine,” which blocks the receptor where
adenosine binds to inhibit the immune cells.
For Dr. Jackson, whose lab is thought to be the world’s best in the
measurement of adenosine and its metabolites, the breakthrough research
is personally deeply rewarding. Fourteen years ago, his older brother,
James F. Jackson, died at 57 of renal cell carcinoma. In 1986, Mr.
Jackson received the National Science Foundation Presidential Award for
Excellence in Science Teaching from Vice President George H.W. Bush.
“Jim was my childhood mentor and the reason I am a scientist today.
His three years of treatment was an emotional and frustrating time for
me because we didn’t have the right tools to help him,” Dr. Jackson
said. “I started doing cancer research because of that experience, and I
hope these results will one day prevent suffering and loss by countless
other families.”
Other study investigators included researchers from the Dana Farber
Cancer Institute, Harvard Medical School and the University of Miami.
The project was funded by National Institutes of Health grants CA 112561, CA 111985, AT 002788, and AI 091693; National Cancer Institute grant 5PO1CA109094-03; and Northeastern University.