Even when surrounded by immune cells, tumors often continue to grow. Their rapid growth consumes oxygen, leading to hypoxia in the surrounding area or tumor microenvironment. Hypoxia further promotes tumor growth by encouraging the release of adenosine, which prevents immune cells from entering the tumor microenvironment. Reducing this immunosuppression in the tumor microenvironment could free immune cells to attack tumors, boosting the efficacy of immune-based strategies for treating cancer.

Now, a research group led by Michail Sitkovsky (Northeastern University, Boston, MA) has shown how this can be accomplished. “Since the root of all problems is the lack of oxygen in tumors, a simple solution is to give tumors more oxygen,” Sitkovsky told NBC News. His group evaluated how oxygen supplementation affected tumor growth and survival in mice with lung tumors. Mice that were placed in a chamber with a gas composition of 60% oxygen showed tumor regression and improved survival compared with mice breathing 21% oxygen, the composition of ambient air (Sci. Transl. Med. 7, 277ra30; 2015). About 40% of tumor-bearing mice breathing 60% oxygen survived 60 days or more, whereas all the tumor-bearing mice breathing 21% oxygen died within 30 days. The anti-tumor effects of oxygen supplementation required the presence of two types of immune cell: T cells and natural killer cells. Hyperoxygenation seemed to inhibit the accumulation of adenosine, allowing the immune cells to infiltrate the tumor microenvironment and attack the tumor, which led to regression and long-term survival.

Supplemental oxygen therapy in cancer has produced mixed outcomes in previous studies. Earlier work using a higher concentration of oxygen (95%) showed toxicity and inflammation, and other reports indicated no benefit of oxygen supplementation, possibly due to a lack of immune cells. Sitkovsky's results indicate that immune cells are required for oxygen supplementation to bring about tumor regression.

Sitkovsky's group proposes that oxygen supplementation, either alone or in combination with immunotherapy, should undergo clinical testing as a cancer treatment but notes several limitations. The regression and survival outcomes observed in the studies required mice to be exposed to 60% oxygen on a continual basis, a requirement that could challenge patient compliance. Furthermore, although inhalation of 60% oxygen is not associated with toxicity and is considered safe in long-term treatments, it can exacerbate injury associated with ongoing acute lung inflammation and therefore should not be used during acute inflammatory episodes.