Second Don't Eat Me Signal Identified in Cancer Cells, Points to New Immunotherapies

Executing merely a function of detecting harmful bacteria and viruses to prevent common cold and flu is not the sole role of our immunity system. Its area of health care services for our body is broad, which we often overlook; especially in case of counteracting the invasion of cancer cells in our bodies.

Until recently we have been aware of the functions of macrophages in identifying cancer cells and neutralizing them to prevent from furthering disastrous activities in our bodies. However, some adamant and aggressive cancerous cells sometimes remain ineffective in the presence of macrophages – a type of immune cell.

Scientists at the Stanford University School of Medicine have discovered a second biological pathway that signals immune systems to not spare cancer cells and kill them. With this new cancer treatment being under trails, it points out to develop new immunotherapies important for fighting cancer. Further, the research believes that by improving the performance of antibody anti-CD47, essential to block the signal ‘don’t eat me’, it shows a promise to develop a new cancer treatment in combination with the newly developed pathway. As a whole, the duo will be able to enhance the immune system, and prevent different types of cancer forms, believes the research head Irving Weissman.

Why Immune cells Fail to suppress cancerous cells?

Macrophages or white blood cells -innate and integral part of our immune system function as scavenger cells. As the name suggests, it scavenges all the infected or cancerous cells by patrolling inside our bodies, and shielding us against all harmful bacteria. This is how macrophages perform to kill cancerous cells and others. However, cancer cells are shielded with CD47 proteins on their surfaces inhibiting the efficacy of macrophages and escape their clutches easily. While coming in contact to a protein called SIRPalpha, CD47 triggers cancer cells to release a ‘don’t eat me’ signal. And they fail to identify them as harmful cells and ignore them.

Ways To Counteract Their Aggressiveness?

A newly discovered second ‘don’t eat me’ signal proves effective in curbing impulsive behavior of cancer cells.

It was discovered several years ago, that an addition of an anti-body protein to CD47, allows both the proteins to stick together and blocks the signaling pathway of CD47/SIRPalpha at the same time. As a result, macrophages will restore their function to identify cancer cells and kills as soon as the anti-CD47 antibody deactivates the ‘don’t eat me signals’ of cancer cells.

It is clear now almost every cancer cell is encapsulated with CD47, so using anti-CD47 proteins; it is possible to suppress the growth of cancer stem cells responsible for different types of cancer growth and tumor relapses.

However, the clinical trials showed that some cancerous cells were aggressive and resistant to antibody anti-CD47and caused dire consequences. Simultaneously, the cancer cells were fewer in numbers too, which responded to these anti-bodies.

In order to find a more strenuous process to neutralize the effects of cancer cells, scientists at the Stanford University of School of Medicine tested surface proteins infused with greater quantity of MHC (Major Histocompatibility Complex) Class I proteins, and found that they were more aggressive and resistant to anti-CD47 antibodies.

MHC class I proteins provide assistance to the branch of the immune system to function properly. 

But, they work differently when it involves cancer cells. These proteins are found to have a control over ‘don’t eat me’ signals of cancer cells. The MHC class I proteins were coaxed to defy ‘don’t eat me’ signals by binding them with LILRB1 proteins found in the macrophages. It was found that when either of the proteins was blocked, the ‘don’t eat me’ signal was curtailed, and macrophage’s ability was restored to identify cancer cells and kill them in the lab setting.

So, it can be said that MHC class I proteins can lend its hand to be used as a biomarker to identify certain types of cancer and bring on a perfect immunotherapy based on this research.