"This paper reveals a metabolic frailty in cancer cells that is based on their own production of oxidizing agents that allows us to utilize existing redox active compounds, like vitamin C, to sensitize cancer cells to radiation and chemotherapy," says co-author Garry Buettner, who was one of the first to propose that cancer cells might have a vulnerability to redox active compounds over 40 years ago. Buettner, along with study senior authors Bryan Allen and Douglas Spitz, are faculty members at the University of Iowa's Department of Radiation Oncology, Free Radical and Radiation Biology Program, in the Holden Comprehensive Cancer Center.

The 11 evaluable patients enrolled in the brain cancer safety trial received three infusions of vitamin C a week for 2 months followed by two infusions per week for 7 months while receiving standard care radiation and chemotherapy. The goal of each infusion was to raise the concentration of vitamin C in a patient's blood to 20,000 μM, as compared to a blood level of about 70 μM found in most adults. The high dose is necessary because vitamin C has a half-life of about two hours in the circulation of humans. The treatment was generally well tolerated; with modest side effects including frequent trips to the bathroom and dry mouth. Rarely, some patients developed high blood pressure that subsided quickly following infusion.

Why is this approach safe? Vitamin C, even at high levels, isn't toxic to normal cells. The research group at Iowa found, however, that tumor tissue's abnormally high levels of redox active iron molecules (a by-product of abnormal mitochondrial metabolism) react with vitamin C to form hydrogen peroxide and free radicals derived from hydrogen peroxide. These free radicals are believed to cause DNA damage selectively in cancer cells (versus normal cells) leading to enhanced cancer cell death as well as sensitization to radiation and chemotherapy in cancer cells.

Higher or lower levels of certain immune cells in cancer patients may be associated with how well they respond to immunotherapy, according to preliminary results of a study conducted by researchers at the University of Pittsburgh Cancer Institute (UPCI).

The findings will be presented today at the American Association of Cancer Research (AACR) Annual Meeting in Washington, D.C., by Robert Ferris, M.D., Ph.D., UPMC Endowed Professor, chief of the Division of Head and Neck Surgery, and co-leader of the Cancer Immunology Program at UPCI.
The research was an extension of the recently completed CheckMate 141 Phase III clinical trial co-chaired by Dr. Ferris, which showed that the immunotherapy nivolumab significantly increases survival and causes fewer adverse side effects in patients with recurrent head and neck cancer.
However, the treatment was not equally effective in all the patients so Dr. Ferris and his team aimed to find out whether differences in the patients' immune system profiles could be associated with better response to immunotherapy.

The researchers found that higher levels of tumor-associated immune cells (TAICs) expressing the PD-L1 protein were associated with longer overall survival and greater likelihood of response to the drug nivolumab. TAICs are immune cells that have infiltrated the tumor and are thought to play an important role in tumor growth.
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In blood samples taken prior to the start of immunotherapy, the researchers also found that patients with higher levels of circulating CD8, or cytotoxic, T cells -- also known as killer T cells -- and lower levels of regulatory T cells were associated with better response to treatment.
"Our study shows that immune cells in the microenvironment around the tumor could play a critical role in how patients respond to immunotherapy. By determining the nature of these cells and how they are affected by treatments, we may be able to significantly improve the effectiveness of current therapies and help a greater number of patients," said Dr. Ferris.

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