The hitherto unknown protein, which the researchers named lymphocyte expansion molecule, or LEM, modulates the proliferation of human T cells as well as in mice, by promoting the proliferation of cytotoxic T cells, which kill cancer cells and cells infected with viruses.
The discovery was unexpected because the new protein had no known function and doesn't resemble any other protein. Researchers from Imperial College London who led the study are now developing a gene therapy designed to boost the infection-fighting cells, and hope to begin human trials in three years.
Cytotoxic T cells are an important component of the immune system, but when faced with serious infections or advanced cancer, they are often unable to proliferate in large enough quantities to fight the disease.
How it happened
By screening mice with genetic mutations, the Imperial team discovered a strain of mice that produced 10 times as many cytotoxic T cells when infected with a virus compared with normal mice. These mice suppressed the infection more effectively, and were more resistant to cancer. They also produced more of a second type of T cells, memory cells, enabling them to recognize infections they have encountered previously and launch a rapid response.
Professor Philip Ashton-Rickardt from the Section of Immunobiology in the Department of Medicine at Imperial, who led the study, said, "Cancer cells have ways to suppress T cell activity, helping them to escape the immune system. 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.
"Next we will test the therapy in mice, make sure it is safe and see if it can be combined with other therapies. If all goes well, we hope to be ready to carry out human trials in about three years."
Citation: I. Okoye et al. 'The protein LEM promotes CD8+ T cell immunity through effects on mitochondrial respiration.' Science, 16 April 2015