Supplemental Oxygen Could Revolutionize Cancer Treatment

Adding supplemental oxygen to cancer immunotherapy could shrink tumors and dramatically increase the survival rate of patients with cancer, according to a new study in Science Translational Medicine.

“We offer experimental and preclinical evidence that supports the conceptually novel motivation to combine systemic oxygenation with current immunotherapies for cancer in order to improve tumor rejection and clinical outcomes,” says lead study author Michail Sitkovsky, Ph.D., the Eleanor W. Black Chair and professor of immunophysiology and pharmaceutical biotechnology at Northeastern University in Boston.
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More than 3 decades in the making, the breakthrough discovery hinges upon Sitkovsky’s prior research—particularly his discovery that the A2A adenosine receptor, found on the surface of immune cells, prevents T cells from invading tumors and deactivates the killer cells that do manage to infiltrate tumors.

“We provided rigorous evidence for an approach whereby using oxygen we can predictably unleash, or reactivate, the previously inhibited anti-tumor T- and natural killer cells so that they are now able to invade and destroy the tumor,” says Sitkovsky, who is also the founding director of the New England Inflammation and Tissue Protection Institute.

He and his colleagues found that inhaling 40% to 60% supplemental oxygen was able to reprogram the metabolism of cancerous tissues away from being hostile to anti-tumor killer cells.

Sitkovsky suggests that these effects could be even stronger if supplemental oxygen were combined with caffeine, a natural A2A adenosine receptor blocker, or a synthetic A2A adenosine receptor blocker he has dubbed “super-caffeine.”

He’s currently collaborating with Graham Jones, Ph.D., professor and chair of Northeastern’s Department of Chemistry and Chemical Biology, to design the next generation of this “super-caffeine” drug, which was originally developed for patients with Parkinson’s disease.

Sitkovsky stresses that oxygen has anti-tumor effects only in combination with cancer immunotherapy.

“This discovery addresses the acute medical need to build on recent successes and further improve the immunotherapies for cancer, which aim to recruit the patient’s own immune cells to recognize, attack, and reject tumors,” he says. “But there is still room to prolong the survival and lessen the side effects.”

He and his colleagues are now orchestrating clinical trials to test this method in the United States and Europe.

—Colleen Mullarkey

Reference

Hatfield SM, Kjaergaard J, Lukashev D, Schreiber TH, Belikoff B, Abbott R, et al. Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Trans Med. 2015 Mar;7(277):277ra30.