New publication: CD47 Blockade Kills Lymphoma Cells Through a Novel Necroptosis Mechanism

We are excited to share that our collaborative work on CD47 immune checkpoint blockade in lymphoid malignancies has been published in the Journal of Hematology & Oncology!

This study, led by co-first authors Stephen J.F. Chong and Rebecca Valentin in collaboration with the Davids Lab at Dana-Farber, reveals a previously underappreciated mechanism by which anti-CD47 antibodies kill tumor cells. While CD47 blockade has long been thought to work primarily by enabling macrophages to phagocytose ("eat") cancer cells, our work demonstrates that anti-CD47 antibodies — including SRF231 and magrolimab — also directly trigger necroptosis, a form of programmed cell death mediated through the RIPK1/MLKL signaling pathway, in diffuse large B-cell lymphoma, Burkitt lymphoma, T-ALL cell lines, and primary CLL patient samples.

This work redefines how we think about the anti-tumor mechanism of CD47 blockade and offers a biologically informed rationale for combining innate immune checkpoint therapy with apoptotic agents in appropriately selected patients with lymphoid malignancies.