In cancer patients, though the body generates tumor-specific antibodies, their efficacy is neutralized by the tumor itself. Tumors recruit cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells, which suppress the body's immune system, thus allowing the tumors to escape immune recognition. Borrello's team has been investigating ways to overcome this immunosuppression.
Suppression of T cells by MDSCs requires, among other things, nitric oxide production. The team reasoned, therefore, that reducing nitric oxide levels might boost immunity in cancer patients. They thus turned to Viagra. Besides its well-known vasodilatory effect, Viagra also reduces nitric oxide production through a separate but linked pathway.
The team gave Viagra to mice with colon carcinoma and found that the immune systems of the mice were indeed boosted. The mice had an increased number of cytotoxic T cells, and tumor outgrowth was reduced by 50–70%. Viagra also provided a boost to T cells transferred to the mice using adoptive cell therapy, with tumor growth being reduced still further.
Viagra, either alone or in conjunction with transferred T cells, did not eradicate the tumors but did significantly slow their progression. Eradication would require a full understanding of the multiple, complex pathways that lead to tumor-induced immunosuppression. In the meantime, the immediate availability of viagra means its potential clinical use can be readily tested.