ANN ARBOR, Mich. — When cancer cells compete with immune cells for glucose, the cancer wins. As a result, the immune T cells are not healthy and don’t have the weapons to kill the cancer.
“If we have a way to manipulate the metabolic pathway, the T cells may be healthier,” says senior author Weiping Zou, M.D., Ph.D., Charles B. de Nancrede Professor of Surgery, Immunology and Biology at the University of Michigan Medical School.
The finding, published in Nature Immunology, suggests a potential metabolic pathway against cancer.
“We know that if we provide glucose, the tumor uses it. One question we have is, can we make T cells resistant to glucose restriction? In our study, we define a mechanism that we can use as a model to test this,” Zou says.
The researchers found that T cells that have stem cell-like properties are tied to longer survival and high tumor killing capacity in human cancer. They propose altering the cancer environmental metabolic pathway to allow the T cells to be largely functional. This would allow the T cells to kill the cancer cells.
Their findings also have potential as a tool to predict ovarian cancer survival, or a marker to predict effectiveness of immune therapy including checkpoint blockade or immune vaccination. Additional clinical testing is needed.
Additional authors: Ende Zhao, Tomasz Maj, Ilona Kryczek, Wei Li, Ke Wu, Lili Zhao, Shuang Wei, Joel Crespo, Shanshan Wan, Linda Vatan, Wojciech Szeliga, Irene Shao, Yin Wang, Yan Liu, Sooryanarayana Varambally, Arul M Chinnaiyan, Theodore H Welling, Victor Marquez, Jan Kotarski, Hongbo Wang, Zehua Wang, Yi Zhang, Rebecca Liu, Guobin Wang
Funding: National Institutes of Health grants CA123088, CA099985, CA156685, CA171306 and 5P30CA46592; the Chinese Ministry of Science and Technology, the Wuhan Union Hospital Research Fund, the Ovarian Cancer Research Fund, Marsha Rivkin Center for Ovarian Cancer Research, Barbara and Don Leclair
Reference: Nature Immunology, “Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction,” published online Nov. 2, 2015