Until recently, the focus of cancer treatment is on killing the cancer cells with medications. These medications are either chemotherapy or targeted treatment (i.e. small molecules that inhibit the growth of cancer cells from within).
Our immune system can control cancer, as we know, of rare cases of spontaneous disappearance of cancers such as early breast cancer, melanoma, kidney cancer, and lymphoma. This was thought to be a result of the activation of our immune system, which recognises the cancer as foreign to our body and eliminates the cancer.
Why do some cancers disappear and some do not?
That is because some cancers are clever enough to produce “inhibitors” to escape our immune system. Therefore, cancer can hide under our surveillance (which is our immunity) and grow unchecked.
What is a normal immune system?
Our immune system is a powerful self defence system. It wards off most infections and identifies harmful organisms as foreign.
It consists of a group of white cells. If you think of these white cells as soldiers in an army, there are different ranks of soldiers and they perform different duties. Some of these white cell soldiers are called antigen presenting cells (APC), T cells, natural killer (NK) cells, B cells and plasma cells.
In general, think of an antigen presenting cell (APC) as a spy. A spy is usually someone who gathers information and process it. APC is the spy in our immune system. It picks up anything from “self” to “non-self”. It identifies “non-self” as foreign and dangerous, be it an infection or cancer, then process it and submit it to a higher “authority” for action.
The higher “authority” is usually the T cells, NK cells and B cells. These cells, once activated, are responsible to kill foreign matters in various ways. NK cells and special type of T cells (called cytotoxic T cells) kill infections or cancers directly. B cells usually tell plasma cells to produce antibodies to neutralise an infection. The communication between all these white cells interactions are mediated by substances called cytokines.
During the entire process, there must be a control mechanism to stop ongoing killing when all foreign matters are eliminated. The signals for stopping are built into the white cells. Some of the important stop signals we have discovered to date are the CTLA-4, PD-1 and PD-L1.
How do cancer escape our immune system?
Cancer is foreign to our body. It is uncontrolled growth of abnormal cells. It is harmful and can attack.
So, how did cancer escape and not being recognised by our APC white cell spies as foreign?
This could be one of two problems – either our immune system cannot see the cancer, or it cannot kill the cancer.
If the cancer does not want to be seen, it can trick our immune system to make more stop signals. One of the signals is CTLA-4. If there are a lot of CTLA-4, the immune system would think that the cancer is “self” and would not recognise the cancer as dangerous (surveillance failure).
Another way for cancer not to be killed by our white cell soldiers is to create another stop signal called PD-L1. When PD-L1 (from cancer) binds to PD-1 (on T cells), it stops the T cells from killing the cancer. So, with the CTLA-4 and PD-1/PD-L1 activated, our immune system is essentially broken because it has failed to see and kill the cancer, and the cancer wins.
Ways to repair and restore our immune system
There are three types of man-made antibodies that are developed and designed to restore our immune system back to normal. These antibodies are sometimes called check-point inhibitors.
1. Anti-CTLA-4: Ipilimumab (Yervoy), is an antibody that binds to CTLA-4, which is a strong stop signal. By stopping the stop signal (releasing the brake), it changes the red robot to green and restores our immune system to see the cancer as foreign.
2. Anti-PD1: Pembrolizumab (Keytruda) and Nivolumab (Opdivo), are antibodies that bind to PD-1. This breaks the PD-1/PD-L1 bond, re-activating the immune cells to kill the cancer.
3. Anti-PD-L1: Atezolizumab, binds to PD-L1 to break the PD-1/PD-L1 bond, activates the killing of cancer.
By restoring or repairing our immune system back to normal, long term control of cancer is possible because our immune system will now recognise cancer as foreign and deal with it appropriately.
Cancers that were deemed deadly, such as melanoma and lung cancer, where survivals are usually less than one year, can now achieve prolonged survival (sometimes in years) and control in up to 40% – 60% of patients with immunotherapy. Side effects are minimal.
These check-point inhibitors are currently under intense investigations and had shown success in the following cancers: melanoma, lung, kidney, bladder, head and neck, certain type of colon cancers and breast cancer, stomach and oesophagus cancers, and lymphomas.
Unfortunately, most of these check-point inhibitors are not registered in South Africa yet, except Ipilimumab for melanoma. The availability of these drugs are either privately funded (with approval from the Medicine Control Council), or accessible via compassionate use programmes. Global clinical trials on immunotherapy are also available at participating centres in South Africa.
We can defeat cancer with our own self defence. As Sun Tzu said in the Art of War, “If you know the enemy and know yourself, you need not fear the result of a hundred battles. If you know yourself but not the enemy, for every victory gained you will also suffer a defeat. If you know neither the enemy nor yourself, you will succumb in every battle”.
Exciting times are ahead for cancer treatment. As we know more about cancer and how it interacts with our immune system, the promise of a cure is near.
Written by Dr Sze Wai Chan.