Leukaemia cells hide behind a sugar coat. Scientists are learning how to strip it away
Blood cancer cells cloak themselves in a layer of sugar molecules that tells the immune system to stand down.
The immune system is supposed to recognise and destroy cancer cells. But cancer is evolutionarily resourceful. Leukaemia cells, it has been known for some time, elevate a protein called CD47 on their surface — a ‘don’t eat me’ signal that instructs immune cells to leave them alone. That’s only part of the story. A commentary published in Science discusses research showing that leukaemia cells also coat their exterior with sialic acid, a sugar molecule found on healthy cells too, but present at abnormally high concentrations on cancer cells.
Sialic acid is not random decoration. It binds to specific receptors on immune cells (called Siglec receptors) that suppress immune activity. The cancer cell is speaking a language the immune system already understands, but using it to pass itself off as safe. The result is that immune cells either ignore the cancer cells or are actively inhibited from attacking them.
Disabling two defence layers at once
What makes the new findings particularly significant is that the sialic acid shield and the CD47 signal appear to work in parallel, reaching the same outcome — immune suppression — through different molecular pathways. That may explain why therapies targeting CD47 alone don’t always work: the cancer cell has a backup strategy.
Researchers are now testing combination approaches that simultaneously target both the sialic acid shield and CD47. Early results in cell culture and animal models are encouraging: disrupting both mechanisms made immune cells substantially more effective at attacking and killing leukaemia cells. Whether this dual approach will work in humans without unacceptable side effects remains an open question — healthy cells also carry sialic acid and CD47, and collateral damage is a genuine concern.
Why age makes this worse
Leukaemia is strongly age-associated. Most forms of blood cancer predominantly affect people over sixty. That’s not coincidental. Ageing degrades immune function — a process called immunosenescence — meaning that cancer cells face less immune surveillance. At the same time, immune evasion mechanisms like the sialic acid shield are themselves a product of selective pressure: cancer cells that evade detection survive longer and proliferate. The result is a double vulnerability: a weakened immune system confronting a cancer that has become increasingly adept at hiding.
Understanding how cancer builds its shield is a necessary step toward therapies calibrated to that aged-immune context. The research is still well upstream of the clinic. But the mechanistic picture it provides is the kind of foundation on which targeted treatments are eventually built.