Macrophages, much like Alice of “Alice in Wonderland,” recognise and consume tumour cells that display “eat me” surface markers.

However, tumour cells can evade detection by macrophages if they successfully present “don’t eat me” signals.

To counter this, researchers have developed drugs aimed at turning off these “don’t eat me” signals.

However, such treatments haven’t been as effective as anticipated in patients with acute myeloid leukaemia (AML) and other blood cancers.

To better understand why, a team of researchers from Mass General Brigham, Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard looked at samples from patients treated for AML at Mass General Brigham.

The team was led by Jooho Chung, MD, PhD, Mounica Vallurupalli, MD, Todd Golub, MD, and Robert Manguso, PhD and the research was published in Science.

The team conducted a genome-scale loss of function screen in AML cell lines, systematically turning off individual genes and cataloguing those that affected detection by macrophages.

Surprisingly, the classic CD47 “don’t eat me” signal had only a weak effect.

Instead, the researchers found that another signal—CD43—had a much stronger influence on macrophage detection.

Their findings suggest that therapies targeting CD43 could be promising for treating patients with AML and, potentially, a broader range of cancers.

Source: Mass General Brigham