Slows Cancerous Tumor Growth

Tripling the amount of oxygen in the air patients breathe could boost the effectiveness of cancer therapies, according to research published Wednesday.

A new study in the journal Science Translational Medicine proposes that adding oxygen to immunotherapy cancer treatments can weaken a tumor’s defenses against cancer-killing cells.

Dr. Michail Sitkovsky, director of the New England Inflammation and Tissue Protection Institute at Northeastern University in Boston, told Healthline that delivering 60 percent oxygen — the amount used in hospitals — could improve tumor rejection by flipping the tumor environment from hostile to permissive.

The solution was embarrassingly simple.
Dr. Michail Sitkovsky, Northeastern University

“The solution was embarrassingly simple,” Sitkovsky said.

Researchers made the discovery while experimenting on mouse models of lung and breast cancers. Mice kept in environments with 60 percent oxygen concentration had a much slower rate of cancer growth compared to mice in regular 21 percent oxygen settings.

This occurred, however, only when the mice also had the tumor-recognizing anti-tumor killer cells prompted by immunotherapy drugs.

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The Link Between Cancer and Oxygen

Cancerous tissues are known to be low-oxygen environments. Not only is it a poor prognosis factor, the lack of oxygen produces adenosine, a molecule that blocks the body’s natural immune response.

Adenosine works against the body’s T-cells and natural killer cells by essentially putting them to sleep so that cancer cells can thrive. Tumors are worse off when adenosine production is decreased or when its effects are blocked.

The new research asserts that the supplemental oxygen decreases production of adenosine by tumors. This “wakes up” the inhibited anti-tumor killer cells to penetrate the tumor and deliver a lethal hit.

When they are given oxygen, the immune killer cells are no longer sleepy or sluggish.
Dr. Michail Sitkovsky, Northeastern University

“When they are given oxygen, the immune killer cells are no longer sleepy or sluggish,” Sitkovsky said.

The paper published Wednesday offers additional therapies to improve the effectiveness of current immunotherapy and cancer vaccines.

“It must be emphasized that oxygen alone won’t help,” Sitkovsky said. “It must be given only together with other treatments that are designed to induce the expansion of anti-tumor killer cells.”

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Targeting Adenosine in the Toughest Cancers

These new findings are the result of three decades of research by Sitkovsky’s team and several groups of leading cancer immunologists.

Studies by John Stagg, Mark Smyth, and others suggest that some of the toughest cancers, including metastatic breast and lung cancers, may be treated more effectively by combining oxygen therapy and similar drugs. These combined therapies can defeat a tumor’s adenosine-based armor.

Sitkovsky said he hopes pharmaceutical companies will take these kinds of low-tech drug options into consideration when formulating immunotherapies.

Researchers are also looking at caffeine as a potential therapy to aid immunological therapies. Prior research shows that caffeine also blocks adenosine receptors. Synthetic versions of caffeine – “super-caffeine,” as Sitkovsky calls them — are used in current Parkinson’s treatments.


Researchers hope to repurpose these existing medications to help increase the effectiveness of cancer treatments.

Oxygen and super-caffeine supplementation with immunotherapy are being researched as cancer therapies because research shows they can reprogram tumors to be supportive of anti-tumor killer cells.

The ultimate goal is to create better clinical results, and, hopefully, fewer side effects.

Supplementing oxygen and synthetic caffeine in cancer treatment is already approved for a randomized, phase one clinical trial.

The study — NCT01799161 — aims to use the gp96-Ig vaccine with theophylline (a natural analog prescribed for asthma and other breathing difficulties) and oxygen to study its effects on lung cancer.

While the 36-month study was initially slated to begin in December, it had to be put on hold due to insufficient funding.

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