Team Identifies a Key Molecule in Immune System Regulation Linked to New Genetic Disease
Source: McGill University Health Centre
Summary: An international team’s work has shed new light on a molecule called TIM-3 that might play a key role in the regulation of the immune response.
Following the 2018 Nobel Prize for Medicine, global attention is now more than ever turned toward the promise of immunotherapy in oncology. Researchers from the McGill University Health Centre have singled out this protein as the next potential target for immunotherapy treatments in patients with cancer and other diseases. Researchers found that when the TIM-3 protein is suppressed or inactive, the immune system becomes completely “unleashed” and T cells are uncontrollably over-activated, resulting in a rare form of lymphoma (a form of cancer that starts in the lymphocytes) called subcutaneous panniculitis T lymphoma (LTSCP). The team of researchers has identified two founder mutations at the origin of this syndrome, which act directly on the TIM-3 protein, preventing it from expressing itself on the surface of the lymphocytes and attacking the cancer cells. The study findings were published in the journal Nature Genetics.
This work was based on findings from the teams at the RI-MUHC and the MCH-MUHC, showing the same rare form of lymphoma in brother and sister. After sequencing their genomes, the researchers discovered that both patients carried the same mutation on a gene called HAVCR2 that codes for TIM-3 and that it was transmitted by their parents. The discovery of this mutation has shed light on a previously undescribed mechanism that allowed us to explain both the clinical presentation and the very particular evolution of these lymphomas under treatment. Researchers are now trying to see if patients with autoimmune diseases such as lupus, a disease where the immune system turns against the body itself may have some TIM-3 dysfunction. There would also be promising avenues for the treatment and understanding of cancers, infectious diseases such as HIV or even malaria as well as multiple sclerosis.
Dr. Nada Jabado said, “For these patients with this rare form of lymphoma, our results reinforce the use of immunosuppressive therapies that will provide much better results and fewer side effects than cytotoxic chemotherapy.”
More Information: Tenzin Gayden et al, “Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome”, Nature Genetics (2018). DOI: 10.1038/s41588-018-0251-4