Oxygen Can Impair Cancer Immunotherapy in Mice

Researchers have identified a mechanism in mice by which anti-cancer immune responses are inhibited within the lungs, a common site of metastasis for many cancers. This mechanism involves oxygen inhibition of the anti-cancer activity of T cells. Inhibiting the oxygen-sensing capability of immune cells, either genetically or pharmacologically, prevented lung metastasis. This research was conducted by Dr. Nicholas Restifo of NCI and colleagues at both NCI and NIAID. The findings appeared Aug. 25 in the journal Cell.

Metastasis is the cause of most cancer deaths. It has long been hypothesized that the process of cancer metastasis requires cooperation between spreading cancer cells and the cellular environment to which they spread. A key component of that environment is the local immune system, which can act to fight off invading cancer cells.

The researchers discovered that T cells, a type of immune cell, contain a group of oxygen-sensing proteins that act to limit inflammation within the lungs. This new research shows, however, that oxygen also suppresses the anti-cancer activity of T cells, thereby permitting cancer cells that have spread to the lungs to escape immune attack and establish metastatic colonies.