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How does higher-risk mds use cd47 overexpression to hide from the immune system?1,2

In higher-risk MDS, a mutated cell may overexpress CD47

CD47 is a checkpoint protein that sends an antiphagocytic, or “don’t eat me,” signal to the immune system.

A graphic of a mutated cell sending antiphagocytic signals.

Overexpressing CD47 suppresses phagocytosis and prevents macrophages from eliminating the mutated cell

Macrophages are part of the innate immune system. They play an important role in the clearance of malignant hematopoietic cells.

A graphic of a mutated cell and CD47 overexpression.

Preclinical data show that CD47 expression is greater in higher-risk MDS than low-risk MDS and may be even greater in AML than higher-risk MDS, making this a key area to focus on in the investigation1,3,4

WHAT EFFECT DOES DIMINISHED CD47 SIGNALING HAVE ON PHAGOCYTOSIS?1

Without CD47 signaling, the prophagocytic receptors on the membrane of macrophages may be able to detect “eat me” signals upon contact with the mutated cell. This could trigger phagocytosis of mutated cells

A graphic of macrophages eating an abnormal cell.

Investigating the immune system may help provide clues in the ONGOING case against higher-risk MDS

The immune system has 2 lines of defense: innate immunity and adaptive immunity5

How can our knowledge of the innate immune system and macrophages help advance the investigation into HR-MDS?

Explore Research Into Higher-Risk MDS
AML, acute myeloid leukemia; CD47, cluster of differentiation 47; HR-MDS, higher-risk myelodysplastic syndrome; MDS, myelodysplastic syndrome. References:
  1. Chao MP, Takimoto CH, Feng DD, et al. Front Oncol. 2020;9:1380. doi:10.3389/fonc.2019.01380
  2. Klei TR, Meinderts SM, van den Berg TK, et al. Front Immunol. 2017;8:73. doi:10.3389/fimmu.2017.00073
  3. Pang WW, Pluvinage JV, Price EA, et al. Proc Natl Acad Sci U S A. 2013;110(8):3011-3016. doi:10.1073/pnas.1222861110
  4. Jiang H, Fu R, Wang H, et al. Leuk Res. 2013;37(8):907-910. doi:10.1016/j.leukres.2013.04.008
  5. Marshall JS, Warrington R, Watson W, Kim HL. Allergy Asthma Clin Immunol. 2018;14(suppl 2):49. doi:10.1186/s13223-018-0278-1
  6. Berraondo P, Minute L, Ajona D, Corrales L, Melero I, Pio R. Immunol Rev. 2016;274(1):290-306. doi:10.1111/imr.12464