"While more than 90 percent of children with ALL in the U.S. become long-term survivors, the outlook remains bleak for patients who relapse.

Searching for an immune response

For this study, Thomas and his colleagues took a closer look at the immune response in children with pediatric ALL. The scientists checked for specialized anti-tumor T cells (CD8+ T cells) that recognize patient-specific mutant proteins. The recognition launches the immune response that kills tumor cells.

Researchers found anti-tumor T cells that recognized 86% of the pediatric ALL mutations and specifically targeted 68% of the leukemic cells. That percentage is far greater than the 2% of solid tumor mutations that anti-tumor T cells are predicted to target.

"Given that we were able to identify tumor-reactive T cells that were functional suggests traditional immune checkpoint inhibitors may not be the best option for these patients," said first author Anthony Zamora, Ph.D., a postdoctoral fellow in Thomas' laboratory. "Cellular-based approaches that allow patients' T cells to be modified to increase the specificity and magnitude of the anti-tumor response could show greater clinical efficacy."

Immunodominance

Thomas and his colleagues made an analogy between viral and tumor immune responses as a possible explanation for the high levels of immune recognition in this study. Large viruses, like high-mutation tumors, produce many possible immune targets. During viral infections, a process called immunodominance leads to a focused immune response that includes production of T cells against a limited number of viral targets.

"The same process may be at work in tumors like pediatric ALL that have fewer mutations," Thomas said. "As a result, the immune system might end up targeting a greater percentage of leukemic mutations, including driver mutations that are responsible for the cancer."

Source: Eurekalert