Checkpoint Inhibitors Are Working But At What Cost?

The immune system in humans is designed to differentiate between normal cells and cells that are seen as foreign invaders. This ability allows the immune system to attack the foreign invaders and leave the normal cells alone. In order to do this, the immune system utilizes checkpoints. Checkpoints are molecules on certain immune cells that need to be activated or inactivated in order to elicit an immune response. It is possible that in some cancers the foreign, or cancer, cells find ways to use these checkpoints to avoid being attacked by the hosts immune system. An example is PD-1 which is a checkpoint protein on T Cells. "It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body." (Immune Checkpoint Inhibitors to Treat Cancer). When PD-1 attaches to PD-L1, a protein on some normal and cancerous cells, it tells the T Cell to leave the other cell alone. It has been shown that some cancer cells have large amounts of PD-L1 which may help them avoid attack. Drugs that target these checkpoints are potential treatments for cancer. 

Checkpoint inhibitors like nivolumab, use antibodies that block the activity of PD-1 on T Cells. Since 2014, there have been five checkpoint inhibitors that block either the activity of PD-1 or PD-L1 which allows the hosts T Cells to attack the cancer. This has been proven to work, but along with attacking the cancer cells, these checkpoint inhibitors are attacking the normal cells as well and causing diseases such as thyroid disease, type 1 diabetes, colitis and other autoimmune diseases. The onset of certain autoimmune diseases may be treatable but a man and a woman in clinical trails with these checkpoint inhibitors died of immune attacks on their heart.

There are a lot of ethical questions raised with the use of checkpoint inhibitors. Even though these drugs are working to cure the cancers, at what cost is it to the patient who may develop an autoimmune disease? As a Physician, how much are you benefitting the patient putting them at risk for one of these diseases? Yes, it is true that they may cure the deadly cancer but the patient may then die from the treatment of the disease that was initially going to kill them. It is very important with these new discoveries that patients be given full autonomy in order to make the most educated decision. 

Science is an amazing and wonderful thing but has so many unknown side effects that need to be fully taken into consideration in order to benefit the whole patient. 

References:

Couzin-Frankel, Jennifer. “Powerful New Cancer Drugs Are Saving Lives, but Can Also Ignite Diabetes or Other Autoimmune Conditions.” Science | AAAS, 16 Nov. 2017, www.sciencemag.org/news/2017/11/powerful-new-cancer-drugs-are-saving-lives-can-also-ignite-diabetes-or-other-autoimmune.

“Immune Checkpoint Inhibitors to Treat Cancer.” American Cancer Society, www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html.