A recent study has uncovered that blocking the immune checkpoint protein CD47, long recognised for enabling immune clearance of cancer cells via phagocytosis, also activates a distinct cell death pathway known as necroptosis. Using advanced techniques across lymphoma and leukemia models, researchers demonstrated that anti‑CD47 antibodies eliminate tumour cells by switching on a molecular ‘death program’ via the RIPK1/MLKL axis.

Importantly, combining CD47 blockade with drugs that block cancer cell survival proteins (such as the BCL‑2 inhibitor venetoclax) proved beneficial in cancers highly reliant on those proteins, but counterproductive in others. Co‑first authored by N2CR member Dr Stephen Chong, this work refines our understanding of CD47 biology and informs rational, patient‑tailored combination strategies in blood cancers.

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