Childhood leukemia could be a target for immunotherapy

Abstract

Pediatric patients with acute lymphoblastic leukemia (ALL) were shown in a recent study to have a strong immune response to their cancer, which suggests that immunotherapy may be helpful in treating the disease. The study, led by St. Jude Children's Research Hospital and published in Science Translational Medicine, indicated that although the cancer has few mutations, antitumor T cells (CD8+ T cells) recognized 86% of pediatric ALL mutations and specifically targeted 68% of the leukemic cells.1 The percentage is much greater than the 2% of solid tumor mutations that antitumor T cells are predicted to target, according to the authors. Because investigators could identify tumor-reactive T cells that were functional, cellular-based immunotherapy approaches that enable T-cell modification would likely be a better option than traditional immune checkpoint inhibitors, according to first author Anthony Zamora, PhD, a postdoctoral fellow in the St. Jude Department of Immunology. The study's findings are key because although 90% of US children with ALL become long-term survivors, those who relapse have much worse prognoses. The robust immune system response in pediatric ALL could potentially be explained by a process called immunodominance, which occurs when the immune system responds to viruses. The process leads to the production of T cells directed against a limited number of viral targets. The same scenario may occur in pediatric ALL and enable the immune system to target driver mutations that are causing the cancer, according to corresponding author Paul Thomas, PhD, a member of the St. Jude Department of Immunology.