(October 15, 2018) This month in Nature, researchers from Weill Cornell published a study that helps to explain why the body’s natural immune response struggles to fight back against ovarian cancer. Using ovarian tumors from humans and mice, they found that T cells, vital to destroying cancerous cells, are inhibited because of the tumor’s effect of the endoplasmic reticulum (ER), which gives the T cells access to one of their energy sources, glutamine. The ER has another function in the tumor environment, which is to use glucose to collect proteins within the cell. When the T cells don’t function properly, the ER can’t function properly either, which signals a stress response by a pathway known as IREa-XBP1. With this pathway in a constant state of stress in addition to having no accessible glucose is detrimental to the T cells.
The team at Weill Cornell, including Juan Cubillos-Ruiz, PhD, the author of the study and OCRA grantee, were able to shut off that pathway in the lab environment. When that pathway was disabled, it allowed the T cells to access the glutamine, which meant it was able to function properly again. In the future, the team hopes that using a drug that inhibits this pathway will allow immunotherapy treatments to be more effective.
“Understanding how chronic stress signals suppress T cell function within tumors is going to be extremely important, particularly for developing the next generation of immune-based treatments for cancer,” says Dr. Cubillos-Ruiz.