Many different cancer treatments work to directly target the tumor or the cells around it. The immediate goal is to mitigate growth and progression, with the hope of complete eradication and long-term durable immunity. However, many barriers prevent complete treatment efficacy. Different proteins and molecules secreted by the tumor polarize the environment around it to allow tumor progression. Unfortunately, the tumor generates an advantageous environment that not only suppresses the immune system, but also dysregulates immune cells to promote the spread of cancer.
Different immune cells around the tumor, such as neutrophils, macrophages, T cells, dendritic cells, and others normally work together to elicit a robust immune response. In the context of cancer, these cells take on a pro-tumor function or are prevented from executing their function. In response, many immunotherapies work to re-activate T cells, which are responsible for eliminating infected cells. Other cancer treatments, such as chemotherapy, works to directly kill the tumor.
While various therapies work through different biological mechanisms, it is still unclear how the tumor uses nutrients to fuel its progression and block immune cell response. Metabolism is the action of a cell that builds and breaks down molecules to provide energy. In general, it has been widely accepted that tumors rely on a metabolic process known as glycolysis to fuel its mass proliferation of cells. Specifically, cells breakdown glucose for energy. Although cancer cells gain energy through glycolysis, there is still a lot that is unclear about cellular metabolism and the influence it has on the environment around the tumor.
A recent article in Nature Cell Biology, by Dr. Gregory Delgoffe and others, demonstrate how tumor metabolism impacts T cell function. Delgoffe is Professor in the Department of Immunology and Associate Director of the Graduate Program in Microbiology and Immunology at the University of Pittsburgh. His work highlights the tumor microenvironment and how T cell function is altered in cancer. Specifically, he investigates tumor and T cell metabolism to expose new mechanisms for cancer treatment.
Metabolic waste created by tumors dysregulates T cell metabolism. To understand which molecules and nutrients are within the tumor microenvironment, the team measured metabolite levels. Delgoffe and others found an increase in phosphoethanolamine, a molecule known to suppress T cell function.  Interestingly, analyzing multiple mouse and human tumors, the team found similar results – a huge quantity of phosphoethanolamine. Researchers are still unsure why this molecule appears in such high quantities, but this discovery provides a possible target to protect T cells from losing their antitumor function.
Delgoffe and others suggest using levels of phosphoethanolamine as a diagnostic tool to determine treatment response and help identify new target drug therapeutics. By understanding what is happening in the tumor, scientists can develop specific treatments. Currently, the research team is trying to understand why there is a buildup of phosphoethanolamine and how to block the effects. Researchers are working to design an effective treatment which could improve T cell function. Overall, this finding provides a biomarker that could help determine optimal treatment regimens prescribed by physicians and open the door to develop novel cancer therapies.
Article, Nature Cell Biology, Gregory Delgoffe, University of Pittsburgh