INVESTIGATING THE IMMUNE SYSTEM MAY HELP PROVIDE CLUES IN THE ONGOING CASE AGAINST HIGHER-RISK MDS

In higher-risk MDS, aberrant bone marrow cells may overexpress immune checkpoint proteins such as CD47, allowing them to hide from the immune system.^1,2

Shining a light on the immune system

The immune system has 2 lines of defense: innate immunity and adaptive immunity.³

• Innate immunity represents the first line of defense against foreign and malignant cells, and acts as a gateway to full and robust immune response by transmitting critical signals to activate the adaptive immune system. The innate immune system plays a critical role in cancer pathogenesis^3,4
• Adaptive immunity refers to antigen-specific immune response. Once an antigen has been recognized as foreign, the adaptive immune system creates immune cells specifically designed to attack the malignant cells³

THE IMMUNE SYSTEM IS COMPRISED OF NUMEROUS CELLS THAT COULD PROVIDE INSIGHTS FOR NOVEL, CLINICALLY MEANINGFUL DISCOVERIES^1,3,5

Macrophages "eat" foreign and malignant cells

Dendritic cells can phagocytose and present antigens from their target to stimulate the adaptive immune system

Natural killer cells release perforin and granzymes to kill tumor cells

B-cells are involved in the creation of antibodies

T-cells are involved in cell-mediated immune responses

There is increasing interest in the activity of macrophages and phagocytic signals¹

Normally macrophages use phagocytosis to clean up abnormal cells, guided by “eat me” signals.

Abnormal cells can protect themselves from phagocytosis by expressing “don’t eat me” signals, such as CD47.

In higher-risk MDS, CD47 is commonly overexpressed, emitting a “don’t eat me” signal that allows malignant cells to hide from macrophages in plain sight.

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