Immunotherapy

As we mentioned in part 1 of our cancer introductory series, there are multiple types of cancer treatments including surgery, radiation and chemotherapy. While these treatments have been around for a long period of time, they aren’t perfect. For example, chemotherapies take a pretty messy approach- imagine if the police were okay with killing a few million civilians in order to get the bad guys… this is exactly how chemotherapy works. Chemotherapy kills cancer cells AND normal cells. Unfortunately, chemotherapy is still one of the most common therapeutic approaches in treating cancer. Chemotherapeutic drugs work by targeting dividing cells, or cells that are reproducing. This includes your hair cells and the cells of your digestive tract, as well as other organs that have slowly dividing cells. This is why we see nasty side effects like hair loss and upset stomach. The hope is that the cancer cells are dividing more rapidly than any other cells in the body, therefore tumor growth will be slowed and all the cancer cells will be killed before all of your normal, healthy cells.     

Another traditional cancer treatment is surgery. Most likely, you understand the concept of surgical removal of tumor(s), a surgeon cuts out all of the cancer cells; however, sometimes surgery is not the best option. The concept of surgery revolves around cutting out and removing ALL of the cancer cells, which is a very difficult task. If even one cancer cell is left after surgery, it could possibly regrow the entire tumor. In some cancers, scientists are finding that surgical removal of a primary tumor increases the risk of a secondary tumor emerging (source). Metastases, or the spreading of cancer to distant sites, can even happen years after surgical removal of the primary tumor. Further, surgery is not always an option for cancer treatment. In order for surgery to work, all of the cancer cells need to form a solid mass. This isn’t always the case. For example, in blood cancers, like leukemia, the cancer cells are flowing all throughout our bodies and, as you can imagine, a surgeon cannot just remove all of our blood to ensure that we are cancer free.

The third traditional cancer treatment is radiation. Radiation therapy uses high doses of energy, similar to X-rays, to kill cancer cells. If you’ve ever had an X-ray for a broken bone, you probably remember using the protective gear to ensure that other parts of your body weren’t harmed from the radiation. Unfortunately, radiation therapy uses the same kind of harmful energy to target cancer; however, during radiation therapy treatment, you are exposed to the high amounts of energy multiple times over a short period, leading to severe side effects. Radiation therapy can irritate the skin, causes severe exhaustion and loss of appetite/ weight loss, weaken the immune system, trigger hair loss and more.  

Current cancer treatments are far from ideal. For many decades, there has been a need for a more natural, less toxic cancer treatment. If you think back to our immunology post, we talked about the “body’s police” or the immune system and how it helps protect our body from “fugitive” cancer cells. There is no doubt that our immune system protects us from far more things than we know. In fact, our immune system kills an average of 10,000 pre-cancerous cells per day (source)! However, our natural immune system is not perfect and occasionally the pre-cancerous cells sneak past the immune system and cancer ensues. Much like drug lords and highly-wanted criminals, cancerous cells try to blend in with the civilians. Many times this involves tricking the immune system into believing the cancer cell is a “self” cell, or a normal cell that should not be attacked. This disguise stops the immune system from attacking the cancer cells because they are trained to leave normal cells, or civilians, alone. When cancer cells disguise themselves and the immune system fails, this is when immunotherapy, an up and coming cancer treatment, could be beneficial. 

Immunotherapy capitalizes on the idea that with an extra “boost”, the immune system’s version of the FBI, the adaptive immune system, can find and attack the fugitive cancer cells. There are several types of immunotherapy, or biological therapy, including checkpoint therapy and cytokine therapy. Checkpoint therapy is aimed at rejuvenating the immune system. As we mentioned, cancer cells can pretend to be normal cells by disguising themselves. One of the most common disguises is by expressing  “self receptor(s)”. Normal cells in our body express one such receptor called PD-L1 (programmed death ligand 1). T cells on the other hand have PD1 (programmed death cell protein 1) on their cell surface. When a T cell is out searching for criminals, fugitives and invaders, it can determine a normal cell from criminals by using the PD1 receptor protein to find and identify PD-L1. When a cell expresses PD-L1, it’s a sign for the T cell not to attack. Cancer cells use this PD1/PD-L1 interaction as a disguise, which stops the police from identifying the cancer cells as fugitives. Now the T cells and the cancer cells sit in a stalemate. In this specific example, a patient could be given an anti-PD-1 drug that would prevent the cancer cell from hiding. We can think of checkpoint therapy, such as the anti-PD-1 drug, as a double shot of espresso for our FBI agents, the T cells. The anti-PD-1 drug sits in the PD-1 receptor on the T cell preventing the PD-1/PD-L1 interaction with the cancer cell. This allows the T cell to identify the cancer cell as foreign and attack. 

A second common type of immunotherapy is cytokine therapy. If you remember back to our immunology post, cytokines are proteins released from cells that  have various jobs. Some cytokines promote inflammation, while others activate immune cells. Interleukin 2, commonly referred to as IL-2, is a cytokine that is known to promote the growth of natural killer (NK) cells and T cells. Both NK cells and T cells play a crucial role in fighting cancer cells, thus, by stimulating the growth of these cells, your immune system has a better chance of finding and killing the fugitive cancer cells. IL-2  was one of the first candidates for immunotherapy and in 1992, IL-2 was approved by the FDA for treatment of metastatic renal cell carcinoma, a type of kidney cancer. Then, in 1998, IL-2 was FDA approved for use in metastatic melanoma, a type of skin cancer. There are numerous other cytokines, some of which are already FDA approved for treating cancers while others are still being evaluated for effectiveness and safety. Overall, cytokine immunotherapy is used to promote or activate your immune system to attack cancer cells.

For decades, traidational cancer treatments have resulted in harsh side effects and painful surgeries. Immunotherapy is a broad term encompassing multiple facets of cancer treatment, and while immunotherapy is far from perfect, it is very promising. Immunotherapy has been shown to work for some patients who have not experienced therapeutic benefit from other therapies. Immunotherapy has also been shown to increase the benefits of other therapies when used in combination therapies. Further, side effects associated with immunotherapy are mild compared to radiation therapy or chemotherapy. Finally, if you remember back to our immunology post, our immune system has a memory, meaning that if the cancer comes back, or relapses, the immune system often recognizes the cancer and acts quickly which can affect overall outcome and survival (source). 

Thanks for reading and make sure to check back next week for the launch of our model organism introductory post! In the meantime, let us know if you have any questions, comments or feedback and don’t forget to follow/ like us!

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Written by Annah & Megan
Illustrated by Rhea

Disclaimer: We are not medical professionals and the above information is not meant to serve as diagnostic factors or medical advice. Further, the opinions in this post are our opinions and in no way reflect the opinions of our mentors or the Medical University of South Carolina.

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