Researchers from Mass General Brigham, Dana-Farber Cancer Institute, and the Broad Institute of MIT and Harvard announced on Apr. 11 that they have identified a new cellular signal that could improve immunotherapy outcomes for patients with acute myeloid leukemia (AML). The study focused on how macrophages, a type of immune cell, recognize and consume tumor cells by detecting certain surface markers known as "eat me" signals. Tumor cells often evade destruction by displaying "don't eat me" signals.
The significance of this research lies in its potential to enhance current cancer treatments. While existing drugs are designed to block these "don't eat me" signals, their effectiveness in treating AML and other blood cancers has been limited.
To investigate further, the team led by Jooho Chung, MD, PhD; Mounica Vallurupalli, MD; Todd Golub, MD; and Robert Manguso, PhD examined samples from AML patients treated at Mass General Brigham. They performed a genome-scale loss of function screen in AML cell lines to systematically deactivate individual genes and observe which changes affected detection by macrophages.
The researchers found that the classic CD47 "don't eat me" signal had only a weak effect on macrophage recognition. Instead, another signal called CD43 was found to have a much stronger influence on whether macrophages detected tumor cells.
These findings suggest that targeting CD43 could offer new hope for patients with AML and possibly benefit those with other types of cancer as well. The discovery may guide future development of more effective immunotherapies.
