Immune check point inhibitors—drugs designed to rouse the immune system against tumors—have revolutionized the treatment of non-small-cell lung cancer. However, many patients don’t respond or obtain long-term benefit. Now, Brendon Stiles, M.D., and colleagues have found a new possible checkpoint: an enzyme known as ART1 that is over-expressed on the surfaces of lung-cancer cells and interferes with the body’s anti-tumor immune response.
In a study published online on March 16 in Science Translational Medicine, researchers analyzed human lung tumors and detected over-expression of ART1 and decreased tumor infiltration by certain CD8 T cells. ART1 was found to interact with a CD8 T-cell receptor, P2X7R, causing the T cells to die. The research team then developed a monoclonal antibody to block ART1’s activity and tested it on mouse models of lung cancer in which ART1 was overexpressed. Compared with mice receiving control antibodies, mice treated with anti-ART1 monoclonal antibodies had fewer and smaller tumor nodules and increased tumor infiltration by CD8 T cells. The findings suggest that targeting lung-cancer tumors with ART1-blocking antibodies could bolster the body’s immune response against lung cancer—and possibly against melanoma, colorectal cancer, and glioblastoma, since evidence suggests that other solid tumors may also rely on ART1 to evade immune attack.
Dr. Stiles, senior and co-corresponding author of the paper, is assistant professor and chief of thoracic surgery and surgical oncology in the department of cardiothoracic & vascular surgery at Albert Einstein College of Medicine and Montefiore Health System. Other co-corresponding authors are Timothy McGraw, Ph.D., and Sandra Demaria, M.D., at Weill Cornell Medicine.
Posted on: Wednesday, March 16, 2022