How do cancer cells evade the immune system?

Cancer cells manage to hide from our immune system (IS) and understanding how they evade the IS helps scientists to create treatments for cancer. It can even help scientists figure out how to hide donor organs in a patient. If you would like to learn more about transplant immunology, click here: https://glamsci.blog/2021/04/13/transplant-immunology/

Usually the IS recognises and destroys any foreign or harmful substance in our body but how does cancer evade this?

What is cancer? 

Cancer is a disease caused by cells that divide uncontrollably. This is the result of mutated cells that have damaged DNA. Instead of developing a super cool mutant power they form tumours. Usually when a cell’s DNA is damaged, the body recognises it and triggers cell suicide (apoptosis) so that the damaged cell doesn’t spread. However, problems with regulation and genes can lead to uncontrolled growth. These cells can spread to other tissues in the body to invade and destroy healthy cells.

Credit: American Association for Cancer Research
Credit: National Cancer Institute

Ways cancer cells evade the immune system 

The T killer cells (type of white blood cell) of the IS regulate the body and get rid of the mutated cells. This stage is known as eliminating phase. At the early stage of tumour growth, the IS does a great job of controlling the development of cancer. However, an equilibrium phase is met when the rate of tumour growth is equal to the activity of the IS. This later develops into the escape phase which is when the cancer cells develop ways to hide from immune cells and survive inside the body undetected. 

Cancer cells have developed multiples mechanisms to evade the IS. Here are a few:

  • Cancer cells inactivate immune cells or change the environment around them so immune cells no longer function. They do this because cancer cells have a protein called PD-L1 on their membrane which is complementary to a PD-1 receptor on an immune cell. These receptors are there to switch off the immune response to regulate it when it is no longer needed, but cancer cells use it to deactivate the IS.
Credit: Harvard University. Checkpoint blockade therapy has been developed which involves antibodies that block the PD-L1 and prevent it from attaching to the PD-1. This means that immune cell will remain active and will be able to kill more cancer cells.
  • The IS has a difficult time recognising cancer cells because they develop from our own cells so it is less obvious that something is harmful if it is not foreign.
  • Cancer cells have higher levels of CD47. CD47 is a membrane protein that binds to a receptor on macrophages (type of immune phagocyte) and reduces it’s ability to kill cancer cells. Scientists are developing Anti-CD47 antibodies that inhibit the binding of CD47 to the macrophage.
Credit: The Royal Society. Here you can see that the CD47 attaches to the SIRPa (receptor on macrophage) which signals to the macrophage not to engulf and destroy it. However, the anti CD47 antibody blocks the CD47 from binding to the SIRPa, allowing the macrophage to engulf it using it’s Fc receptor.
  • Cancer can spread to the bone marrow (where white blood cells, a type of immune cell, develop) which weakens the IS. This is common in cancers like leukaemia and lymphoma.

There are many more mechanisms that are being researched to target cancer cells and develop immunotherapy treatment where scientists can stimulate the IS to attack the cancer itself (I have explained some, such as the anti-CD47 antibodies and checkpoint blockage therapy). There is also another post on cancer vaccines here: https://glamsci.blog/2021/01/03/anti-cancer-vaccines/

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