I remember being mind blown when I first read about how Harry Potter was able to disappear into alleys by wearing his invisibility cloak. The idea that someone could hide in plain sight always fascinated me as a child. What if I said that this happens right in the human body, where certain cells are able to use an invisibility cloak to camouflage themselves? You read it right: cancer cells have this extraordinary ability to hide in plain sight in the body. But, scientists are working on ways to get cancer cells to come out of hiding and to target them for destruction.
To understand how cancer cells camouflage themselves, we have to start by examining how our body detects cells that are not supposed to be there. Our body is equipped with a powerful defense mechanism made up of immune cells. T-cells are a type of immune cell that act like warriors, detecting and destroying any suspicious-looking foreign cells. When a bacteria or virus enters the body, the substances released by them, called antigens, are picked up by another type of immune cell, known as antigen-presenting cells (APCs). These APCs display the foreign antigens on their surface to show T-cells that a malicious cell was detected. T-cells have receptors on their surface that can engage with these antigens on foreign cells and kill them. So in this case, why are cancer cells not simply destroyed by this army of T-cells? We must keep in mind that cancer is not caused by a foreign invasion. Instead, cancer cells are our own body cells that have gone rogue due to various undesired mutations.
T-cells undergo a process of maturation, when they are strictly trained to differentiate cells as self and non-self in order to prevent them from harming normal body cells. When the receptor on a T-cell detects a self cell, it ignores the cell and gets deactivated. The normal body cells produce a protein known as PD-L1, which works like an ‘identity card’ and prevents them from being destroyed by T-cells. The ever-evolving cancer cells, however, have learned to use this to their advantage by producing PD-L1 in excess on their surface. Now, when the receptor PD-1 on a T-cell detects the presence of PD-L1 on a cancer cell during immune surveillance, it is convinced that the cancer cell is a normal cell and it is left unharmed. This is one example of the process called immune checkpoint, wherein cancer cells apply a brake on T-cell mediated killing.
Scientists have been working for decades to make cancer cells come out of hiding and make them visible to immune cells for destruction. In 2018, the Nobel Prize in medicine was awarded jointly to immunologists James Allison and Tasuko Honjo for their contributions to cancer immunotherapy. They both independently discovered different immune checkpoint mechanisms that can be targeted to eliminate cancer cells. Honjo discovered the checkpoint mechanism mediated by PD-L1, while Allison discovered a similar mechanism mediated by another molecule known as CTLA-4.
Cancer immunotherapy involves using ‘immune checkpoint inhibitors’ to suspend the brakes that stop T-cells from killing cancer cells. One example is the drug Durvalumab, a monoclonal antibody that can specifically bind to the immune checkpoint molecule PD-L1. Binding of PD-L1 prevents its interaction with T-cells, which blocks the immune checkpoint and allows T-cells to kill the cancer cells containing PD-L1. Durvalumab has been approved for immunotherapy by the FDA (US Food and Drug Administration) for urothelial bladder cancer and has shown promise in early-stage studies for the treatment of non-small cell lung cancer and head and neck cancers. Cancer immunotherapy has been gaining popularity due to its great success in advanced melanoma, or cancer of the melanin pigment-producing cells; and its innovative mechanism of action, which uses the immune system to target cancer cells.
But, like any other cancer therapy, there is never a “one size fits all” treatment plan. Immunotherapy works like a charm for some cancers, but sadly, it is not as effective in all cases. Research has shown that not all cancers are susceptible to immunotherapy. The success rates for some cancers, such as colon cancer and breast cancer, are very low. Another potential concern with using immunotherapy is the side effects that may be caused by it. Since immunotherapy fundamentally makes cancer cells more susceptible to attack by immune cells, it poses a risk of revving up the immune system. Thus, immunotherapy could lead to an increase in inflammation and cause itching, flu-like symptoms, and fatigue.
There is no doubt that immunotherapy is a boon to cancer patients who have been able to benefit from it. But, continued research is essential for spreading the net of immunotherapy to different cancer types. Also, strategies to overcome the side effects caused by an overactive immune system need to be developed.