Biologists Identify a New Approach to Cancer Immunotherapy

A New Approach to Cancer Immunotherapy

Yale researchers have found a way to boost immune response by “rewiring” immune cells that metabolize the most glucose, giving them an advantage in the battle against cancer cells inside tumors.

Scientists from Yale University have identified a new way to boost immune response by metabolically “rewiring” immune cells.

Inside a tumor, immune cells and cancer cells battle for survival. The advantage may go to the cells that metabolize the most glucose, say Yale researchers who have identified a new way to boost immune response by metabolically “rewiring” immune cells.

Their research, published August 27 online in Cell, may provide a novel approach to cancer immunotherapy.

Researchers have long known that specific immune cells known as T cells infiltrate tumors. But tumor-infiltrating T cells fail to destroy cancer cells, in part, because inside the tumor they are deprived of glucose, a nutrient essential to T cell function. The research team, led by professor of immunobiology Susan Kaech and postdoctoral fellow Ping-Chih Ho, theorized that metabolic reprogramming of T cells could enhance their anti-tumor response.

When cells eat glucose, they convert it into a metabolite called phosphoenolpyruvate (PEP). Using biochemical analyses, the researchers identified a new role for PEP in fine-tuning the anti-tumor response of T cells. They genetically reprogrammed the T cells to increase PEP production, restoring cell function and slowing tumor growth.

The research reveals a potential new form of cancer immunotherapy. “Knowing how the metabolic state of T cells is affected in tumors, we may find new ways of altering their metabolism to make them more efficiently kill tumor cells,” says Kaech. These types of approaches could be directly applied to clinical trials using adoptive T cell therapy, she notes.

The study results may also apply to conditions other than cancer. “Understanding how immune cell metabolism affects their function could lead to novel approaches to adjust immune responses in a variety of diseases,” says Ho.

Reference: “Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses” by Ping-Chih Ho, Jessica Dauz Bihuniak, Andrew N. Macintyre, Matthew Staron, Xiaojing Liu, Robert Amezquita, Yao-Chen Tsui, Guoliang Cui, Goran Micevic, Jose C. Perales, Steven H. Kleinstein, E. Dale Abel, Karl L. Insogna, Stefan Feske, Jason W. Locasale, Marcus W. Bosenberg, Jeffrey C. Rathmell and Susan M. Kaech, 27 August 2015, Cell.
DOI: 10.1016/j.cell.2015.08.012

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