Flipping A Genetic Switch on Cells Lets Researchers Boost or Suppress Immune Responses
Research Points Toward Immunotherapies for Cancer and Autoimmune Diseases
By Nicholas Weiler | UCSF.edu | May 1, 2020
Cancer and autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, might not seem to have much in common, but some researchers now are pinning hopes on the same immune system cell – called the regulatory T cell, or Treg – to better fight both, through immunotherapies that manipulate these cells in opposing ways to fight the two disease types.
A key role of Tregs is to dampen the destructiveness of another type of T cell, called an effector T cell, a warrior cell that actively targets invading pathogens and tumors. By calming T effectors, Tregs help the immune system return to a normal level of guardedness after a vigorous battle against infection has been won. Autoimmune disease has been linked to weak Treg responses that fail to fully restrain effector T cells, allowing them to attack the body’s own tissues. In contrast, in many common types of tumors, high levels of suppressive Tregs in the vicinity of the cancer can prevent the immune system from attacking the tumor, which has been linked to worse outcomes.
In a new study published on April 29, 2020, in Nature, UC San Francisco and Northwestern University scientists identified genes with the potential to be manipulated clinically as a kind of switch for Tregs. Flipped one way by perturbation of a gene, the switch can drive Tregs to allow the immune system to more vigorously attack rogue cancer cells within the body. Flipped the opposite way, by perturbing a different gene, the switch may keep the immune system from attacking the body’s own tissues in autoimmune diseases.
“Tregs exerting their normal suppressive function can prevent your immune system from fully tackling cancer, but we found a way to flip a switch to dampen that suppression resulting in an enhanced anti-tumor immune response,” explained UCSF graduate student Jessica Cortez, a lead author of the new study, who conducted many of the experiments in the lab of senior co-author Alexander Marson, MD, PhD, a UCSF immunologist.