Cancer is a disease in which some of the body's cells go rogue, spreading uncontrollably to other parts of the body and leading to functional disruption of normal processes in tissues and organs, and eventually to death. In 2020, an estimated 19.2 million people worldwide were diagnosed with cancer, and almost 10 million people died the same year from this devastating cause -- around 1 of every 6 deaths worldwide.
In 1957, Burnet and Thomas proposed the "immuno-monitoring" hypothesis, suggesting our body is constantly on the alert -- searching and killing any "rebel" cells of our own to maintain a homeostatic environment. Our immune system reacts to various tumor-specific as well as non-tumor-specific antigens expressed by malignant or damaged cells and kills such cells. The anti-tumor immunity is enabled by an army of professional bodily "guards" -- macrophages, T-cells, natural killer cells and other important effector cells. However, cancer cells are particularly "smart" at escaping the fierceness of our immune system by utilizing a variety of mechanisms.
One key mechanism cancerous cells use to deceive our immune system is by overexpressing CD47, a signaling molecule which is widely regarded as a "don't eat me" message for the macrophages and other immune cells. Under normal physiological conditions, our healthy cells use this protein molecule routinely as a means of maintaining peace with an otherwise highly aggressive immune system. CD47 protein interacts with another important player in this process -- signal regulatory protein α (SIRPα), a membrane glycoprotein present on the surface of some immune cells (myeloid cells) -- leading to a negative control of the innate immune cells.