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bioRxiv · 10.64898/2026.07.25.740652

Beyond Immune Evasion: CD47-Driven Pro-Tumorigenic Dysfunction in Diffuse Large B Cell Lymphoma and Triple-Negative Breast Cancer

Lum, T. C. I.·Tan, J. Y. M.·Ng, F. J. H.·Leong, S. M.·Bin Masroni, M. S.·Hue, S. S. S.
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Abstract

Abstract/SummaryCD47 is a ubiquitously expressed transmembrane protein that functions as a negative immune checkpoint, marking host cells as "self" by delivering an inhibitory "dont-eat-me" signal to phagocytes. Cancer cells co-opt this mechanism, upregulating CD47 to evade immunosurveillance and phagocytosis by innate immune cells, a pattern observed across solid tumours and haematological malignancies. CD47 overexpression correlates with poor prognosis across most cancer types, including therapy-resistant disease. Despite extensive efforts to develop CD47-targeted therapies, the downstream biological consequences of aberrant CD47 expression within tumour cells remain poorly characterised beyond its established anti-phagocytic role. This study investigated non-immunological, pro-tumorigenic functions of CD47 to define the cellular effects, beyond immune evasion, that CD47-targeted therapy might disrupt. We found that CD47 exerts cancer type-specific effects: in DLBCL, CD47 loss impaired mitochondrial metabolism and sensitised cells to R-CHOP standard-of-care chemoimmunotherapy, whereas in triple-negative breast cancer (TNBC), CD47 knockdown delayed cell cycle progression, enhanced migration, and conferred resistance to specific chemotherapeutic agents. These findings indicate that CD47 has multifaceted, context-dependent roles in tumour biology that extend beyond immune checkpoint signalling. Clinically, this suggests CD47-targeted therapies may produce cancer type-specific off-target effects on tumour metabolism, proliferation, and drug sensitivity, which are considerations that should inform their rational combination with existing targeted therapies.

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Lum, T. C. I., Tan, J. Y. M., Ng, F. J. H., Leong, S. M., Bin Masroni, M. S., Hue, S. S. S.. 2026-07-27. Beyond Immune Evasion: CD47-Driven Pro-Tumorigenic Dysfunction in Diffuse Large B Cell Lymphoma and Triple-Negative Breast Cancer. https://doi.org/10.64898/2026.07.25.740652

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