The Immune System & How It May Provide Clues Into MDS

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 investigation^1,3,4

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

Innate immunity represents the first line of defense against foreign and malignant cells, and acts as a gateway to a full and robust immune response by transmitting crucial signals to activate the adaptive immune system. The innate immune system plays a critical role in cancer pathogenesis^5,6 Key cells include: macrophages, dendritic cells, natural killer cells

Adaptive immunity refers to antigen-specific immune response. Once an antigen has been recognized as foreign, the adaptive immune system creates immune cells designed to attack the malignant cells⁵ Key cells include: B-cells, T-cells

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:

Chao MP, Takimoto CH, Feng DD, et al. Front Oncol. 2020;9:1380. doi:10.3389/fonc.2019.01380
Klei TR, Meinderts SM, van den Berg TK, et al. Front Immunol. 2017;8:73. doi:10.3389/fimmu.2017.00073
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
Jiang H, Fu R, Wang H, et al. Leuk Res. 2013;37(8):907-910. doi:10.1016/j.leukres.2013.04.008
Marshall JS, Warrington R, Watson W, Kim HL. Allergy Asthma Clin Immunol. 2018;14(suppl 2):49. doi:10.1186/s13223-018-0278-1
Berraondo P, Minute L, Ajona D, Corrales L, Melero I, Pio R. Immunol Rev. 2016;274(1):290-306. doi:10.1111/imr.12464

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

WHAT EFFECT DOES DIMINISHED CD47 SIGNALING HAVE ON PHAGOCYTOSIS?1

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

WHAT EFFECT DOES DIMINISHED CD47 SIGNALING HAVE ON PHAGOCYTOSIS?¹

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