Cytotoxic CD8+ T cells are an essential cog in the immune system mechanism, since their role is to kill infected or transformed cells and protect the host from intracellular viruses and cancer. Yet, when faced with serious infections or advanced cancer, the body is often unable to generate large enough quantities to mount a sufficient counter-offensive. However, scientists at Imperial College, London and their colleagues have discovered a protein they believe plays an integral role in promoting immunity to viruses and cancer.
This discovery caught researchers by surprise since the new protein had no previously known function and doesn’t resemble any other known proteins. However, when the scientists used the protein, which they dubbed lymphocyte expansion molecule (LEM), in mice and on human cells in vitro they observed a significant increase in the proliferation of cytotoxic CD8+ T cells.
The findings from this study were published recently in Science through an article entitled “The protein LEM promotes CD8+ T cell immunity through effects on mitochondrial respiration.”
“Cancer cells have ways to suppress T cell activity, helping them to escape the immune system,” explained Philip Ashton-Rickardt, Ph.D., professor in the department of medicine at Imperial College and senior author on the study. “Genetically engineering T cells to augment their ability to fight cancer has been a goal for some time and techniques for modifying them already exist. By introducing an active version of the LEM gene into the T cells of cancer patients, we hope we can provide a robust treatment for patients.”
Dr. Ashton-Rickardt and his colleagues screened mice with genetic mutations and discovered a strain that produced 10 times the number of cytotoxic T cells when infected with a virus than normal mice. Furthermore, not only did the investigators find that the mice were able to suppress the viral infection more efficiently than wild type mice, they were also more resistant to cancer and produced significantly higher numbers of memory T cells. Using high-throughput exome screening the researchers were able to identify that the LEM gene was responsible for the protective effects they observed.
“This study has identified the novel protein LEM and unlocked an unexpected way of enhancing the ability of our immune system to fight viruses or cancers,” said Claudio Mauro, Ph.D., research fellow at the William Harvey Research Institute in Queen Mary University of London and co-author on the study. “This is based on the ability of the protein LEM to regulate specific energy circuits, and particularly mitochondrial respiration, in a subset of white blood cells known as cytotoxic T cells. This discovery has immediate consequences for the delivery of innovative therapeutic approaches to cancer.”