Introducing your IRL Superhero-in-Training: IL-2
When you think of superheroes, you probably imagine some buff guy or gal wearing a fancy costume who delivers a lot of catchphrases while fighting bad guys.
Well, you’re not wrong. The dictionary even agrees with you.
What if I told you that there were real-life superheroes?
Now, I’m aware that we currently don’t have alien monsters (or even aliens 👽) wandering about in the streets. But think about it. In reality, a superhero is nothing more than someone who saves lives.
Maybe, a superhero can even be something.
Enter IL-2: A cytokine that is being used as an immunotherapy for cancer.
If the above sentence sounded like gibberish to you, you’re not alone. But don’t worry! By the end of this article, that sentence will be as clear as day. You’ll have an in-depth understanding of the world’s very own Superhero-in-Training. You’ll learn about everything from the second most complex system in your body to the disease that is Canada’s leading cause of death.
Hooked? Let’s get into it.
If you’re feeling lazy, scroll to the bottom for a TL;DR section!
Part One: The Immune System
Unfortunately, IL-2 is one of those subjects that you need to learn an entirely new concept to understand. We’re going to take a quick detour and learn about the immune system. Trust me, it’ll all be worth it in the end.
The immune system exists to protect your body from pathogens. Pathogens are any microorganism that could potentially cause disease. An organism becomes a pathogen when it successfully bypasses your skin or mucous membrane. Some examples of pathogens include bacteria, viruses, and parasitic worms (which are the most disgusting creatures on Earth🤮)
The immune system is composed of the innate immune system and the adaptive immune system.
The innate immune system is your body’s first line of defense after the skin or mucous membrane. It is non-specific, meaning that the innate immune system’s “weapons” aren’t specifically tailored to target a certain pathogen.
If a situation gets too hairy for the innate immune system, the adaptive immune system will be activated to join the fight. The adaptive immune system has specific counter weapons to whatever pathogen it’s facing 🤯! And when I say whatever, I mean whatever.
IL-2 fits into the innate immune system. But before we are officially introduced to IL-2, let’s introduce the whole team. Or should I say… squad?
The Members of the Innate Immune System: The Suicide Squad
Imagine that you’re on your way home from school. You’re having a pretty good day! The weather’s nice and you did well on that test you thought you were going to fail.
As you look up from your phone, you see your bus zoom past you. You begin to panic as you realize that you may need to walk home. But there’s still hope! You begin to run like your life depends on it, faster than ever before. The bus doors open and people hop aboard while you keep on running. You’re less than a block away as the last people begin climbing onto the bus. Then suddenly, you go flying and scrape your knee upon landing on the sidewalk. You look back to see the culprit: a small rock. As you collect yourself and begin desperately limping towards the bus, the doors close and leave without you. Not only will you need to walk home, but now you have to do it with a bleeding knee 😑
For you, it’s not a big deal, just a nuisance. While you grumble and begin the long walk home, your immune cells are fighting a suicide battle to protect you from the bacteria that invaded through your injury.
Here’s a rundown of the soldiers and what they’re up to on this bloody battlefield:
- Macrophages are a type of phagocyte (a cell that “eats” pathogens) that swallows any pathogens that they find. Then, rather than digesting the pathogen, they will tear it up into a thousand tiny pieces. The leftovers of the pathogen are called antigens. The macrophage will then expel these antigens for the dendritic cells to analyze (more on this later!). This process is called phagocytosis.
- Mast cells are like the world’s most sensitive bombs. Once a mast cell comes into contact with a pathogen or an antigen, they immediately begin releasing chemicals such as histamine that can cause rapid inflammation. Mast cells are responsible for allergic reactions. They can be hyper-sensitive to allergens (antigens that possess no harm) and let out chemicals that end up causing inflammation. That’s why bad allergies can be so severe! If this happens in someone’s airway, there’s a chance that they’ll die.
- Neutrophils are called onto the job if the macrophages and mast cells need more help. Like macrophages, they’re also classified as phagocytes. Neutrophils are nuts. And not in a good way. Think of them as drunk soldiers who are aimlessly firing not one, but two, machine guns. It’s safe to say that you wouldn’t trust this guy to protect you. So how is this analogy relevant? Without getting into too much detail, neutrophils can each use their DNA to form a Neutrophil Extracellular Trap (NET). These NETs are like whips that neutrophils use to kill pathogens. The problem with this is that they can accidentally harm your normal cells instead of the enemy, which happens more often than not. This is why neutrophils only have a limited time to fight before being forced to commit controlled cell suicide, also known as apoptosis.
- Dendritic cells are the (only) brains of this chaotic mess. They wander the battlefield, collecting samples of the antigens that the macrophages left behind for them. If a dendritic cell sees that the innate immune system is losing the battle, it can activate the adaptive immune system for more specific weaponry. In terms of an army, the dendritic cells are the generals of this mission.
We’ve spent a lot of time talking about the fighter cells, but soldiers aren’t the only part of an army! It’s time to spotlight the messengers of the immune system: the cytokines.
Cytokines: Your Destination’s on the Right
You’d think that the macrophages, neutrophils, and mast cells would have to be able to see, right? How else would they know where the pathogens are?
Interestingly enough, these cells don’t have any form of detecting pathogens, meaning they can’t see 👀. So how would they know where pathogens are?
This is the responsibility of the cytokines. Cytokines carry information from cell to cell. They use this ability to function as the GPSs for your cells: they direct immune cells to the site of the danger 🗺
Let’s go back to your grazed knee.
A macrophage is wandering about, enjoying its day when a bunch of bacteria begin swarming in as your skin rips open. The macrophage knows this is bad news and begins devouring the bacteria. But there are just too many now for it to defeat alone. So, the macrophage sends out some cytokines into the lymphatic system. These cytokines carry an important message: “Danger! Backup needed! S.O.S!”
Meanwhile, a dendritic cell is strolling through the lymphatic system, looking for anything out of the ordinary. It sees cytokines floating about, so it approaches them and, for lack of a better word, “inhales” the information. The dendritic cell uses the density of cytokines in that area as a navigation guide. Think of this like using a ringtone to find your phone; the louder the sound, the closer you are. Once it arrives at the battlefield, it joins in and begins doing its job, in this case taking samples.
This cycle repeats for any other immune cell that “inhales” the cytokines, even cells that we haven’t covered in this article.
So, why is all of this relevant?
IL-2: The Origin Story
Time to review that introductory sentence on IL-2. I described it as “a cytokine that is being used as an immunotherapy for cancer.”
Do any of those words stick out to you now?
If you missed it, the point here is that IL-2 is a type of cytokine. That means we know a bit about what IL-2 is!
IL-2 is short for interleukin 2. This specific type of interleukin is responsible for immune responses.
Okay, but how do interleukins fit into cytokines and what’s the 2 for? Well, let’s compare IL-2 to apples 🍎. Apples are fruit and there are different types of apples. Cytokines would be the “fruit” class, interleukin would be the apples, and 2 would be the specific type of apple, say a red one.
Another example would be dogs 🐶: dogs are animals and there are different breeds. Cytokines would be the “animals” class, interleukin would be the dogs, and 2 would be a breed of dog. It’s kind of like a taxonomy system for cytokines!
Congrats! You’ve made it through part one, which is the hardest part of this article. Since that was a lot of information to take in (especially if you’re new to this), here’s a quick summary of what we’ve learned:
- The immune system protects your body from microorganisms that have bypassed either your skin or mucous membrane, aka pathogens
- The immune system is made up of two parts: the innate immune system and the adaptive immune system
- The innate immune system is the first to begin fighting pathogens. It is non-specific, meaning it isn’t made to fight a specific pathogen
- The adaptive immune system arrives if the danger grows too large. It is specific, meaning it has a way to defeat every single pathogen that could invade you
- Important cells in your innate immune system are macrophages, mast cells, neutrophils, and dendritic cells
- For the immune cells to communicate with each other, they rely on cytokines, a type of protein that carries information
- IL-2 is short for interleukin 2, which is a type of cytokine
We’ve talked a lot about the hero of our story, but who’s the villain? It’s about time we introduced them.
Will there be any more superhero gifs? You bet 😏
Part Two: Cancer and Immunotherapy
Cancer. The disease that’s been plaguing society since day one, yet most people don’t understand it! Kind of like how only comic fans recognized the big purple guy with a weird chin at the end of Avengers and then next thing you know, he’s the big bad for the two highest-grossing superhero flicks of all time 🎥.
I know that a villain’s a victim whose story hasn’t been told, but whoever said that hasn’t met cancer.
Now, I could go over cancer here… but I’ve already written an article on it that you should go check out right now!
Don’t feel like reading another article? No worries, I’ve got you covered (though I’d still recommend reading the article):
- Cancer happens when an error in a cell’s DNA causes it to continually multiply without stopping. It’s similar to when some code has a bug: one tiny error causes the entire program to flip on its head. The genetic code is altered in a way so that cancer cells can’t commit apoptosis (controlled cell suicide, not crazy neutrophil suicide)
- Tumors are formed when cancer cells clump together
- Tumors can either be benign (stays in one place) or malignant (can move to other places in the body through a process called metastasis)
With the basics out of the way, I want to ask you a question: if cancer is our Thanos, then who are the Avengers?
“Wait,” you say, “the immune system, right? Can’t it take care of cancer on its own?”
Well…
Immunotherapy: The Super-Team’s Drugs
Here’s the thing: the cancer cells’ sudden takeover with their army of clones means that the immune cells have no wiggle room. This leads to the immune cells being squished to death.
The remaining immune cells need some backup. There’s no way that they could face all these cancer cells alone. So, who do they call? (Hint: it’s not the ghostbusters 👻)
Well, that was a trick question. Sort of. The immune cells don’t call anyone, but the doctors do. They enlist the help of immunotherapy.
Immunotherapy is used to boost the immune system. Immunotherapy is typically injected into a patient. Some immunotherapies can slow down, or even stop, cancer’s expansion. Others can enhance immune cells’ performance against cancer cells, kind of like the drugs that bodybuilders use to make them stronger. There are even some that bring toxins, such as chemotherapy, to cancer cells!
And wouldn’t you know, IL-2 is also a form of immunotherapy!
It’s time to merge all of our knowledge to make some real food for thought.
Part Three: IL-2 vs Cancer
You know, this article’s shaping up to be like a superhero movie. We’ve got our hero. We’ve got our villain. We’ve got the first and second acts setting up the big final fight… the third act.
Before we begin, I want to mention that current studies have been focusing on using IL-2 primarily against metastatic melanoma (metastatic skin cancer) and metastatic renal cell carcinoma (metastatic kidney cancer). Therefore, IL-2 may not be as effective or ineffective in other types of cancers.
Applications of IL-2: The Fighting Styles
IL-2 as immunotherapy can be used in numerous ways. Think of these ways as different fighting styles. All of these fighting styles have two things in common: they are non-specific immunotherapies and assist the immune system. This is mainly by helping to increase the amount of T cells and Natural Killer cells in the body, which are part of the adaptive immune system (remember, the part of the immune system that has specific weapons for every pathogen that could invade you).
These are the fighting styles that scientists have experimented with so far:
- IL-2 as monotherapy (IL-2 on its own). This one isn’t commonly used anymore. Instead, we are using IL-2 combined with other treatments
- IL-2 with other cytokines. We already covered cytokines in this article, but in case you forgot, cytokines are the messenger pigeons of the immune system
- IL-2 with cell-based immunotherapy. Cell-based immunotherapy helps immune cells recognize tumor antigens (which are normally very sneaky and hard for them to detect) so they can destroy the cancer cells
- IL-2 with chemotherapeutic agents. Chemotherapeutic agents target specific phases in the cell cycle (the process of a cell dividing) to refrain the cancer cells from multiplying
- IL-2 with targeted therapy. Targeted therapy is quite simply, an immunotherapy that is specific to a certain type of cancer or antigen. An example of this would be the EGFR mutation in non-small-cell lung cancer
- IL-2 with peptide vaccines. Peptides are a type of amino acid, which is a molecule that forms proteins. They can mimic the qualities of an antigen, thus creating an immune response
- IL-2 with immune checkpoint inhibitors. Immune checkpoint inhibitors are essentially security checks run by T cells to make sure that there aren’t any immune responses that could kill healthy cells
All of these treatments showed promising signs and were able to defeat metastatic cancers. Plus, trials proved that there were benefits to using IL-2. For example, patients had higher response rates when using high-dose (HD) IL-2 combined with other treatments compared to IL-2 on its own. There’s a lot of information to go through here, so if you want a more detailed run-through, check out this article (also in the works cited).
Why do we need IL-2 though? Don’t we already have chemotherapy and radiotherapy?
That’s true. The problem with these treatments is that they not only destroy cancer cells but normal cells as well. It’s like using a tornado to wipe out some unused buildings. You’ll destroy the unused buildings but you'll destroy all the other buildings as well.
Well, great! IL-2 must be a perfect cancer treatment then! It sounds like we’ve finally eradicated cancer!
Unfortunately, that’s not the case. What are the cons of IL-2?
The Weaknesses of IL-2
I mentioned HD IL-2 in the section above. The reason that we have to use HD IL-2 is that low-dose IL-2 doesn’t pack enough of a punch 🥊. Studies have shown that HD IL-2 had longer response durations and higher response rates than low-dose IL-2 combined with other cytokines (specifically a cytokine called interferon a). But using HD IL-2 has its problems.
For one, HD IL-2 has high levels of toxicity that can harm people rather than help them. The other reason is that HD IL-2 is like a double-edged sword; it can enhance the immune system’s response against tumors or it can hinder it. When HD IL-2 is used, T regulatory cells (Tregs) over-expand and limit anti-tumor responses.
A possible solution to this problem is to find IL-2 mutants that can activate Natural Killer cells and effector T cells without an increase in Tregs. This would allow for the immune system to activate anti-tumour without Tregs getting in the way.
In conclusion, IL-2 does have the potential to be the holy grail of cancer medicine, but there’s still some work to do before we get there.
In my short 13 years of existence, I have seen multiple loved ones pass due to cancer. My grandfather. My grandmother. And worst yet, my younger brother.
None of them had access to the medications that we’re developing today.
In reality, most people you’ve met have probably lost at least one person they know, someone they care about, to cancer.
Humans aren’t built to take that much pain. Nor is our society.
The world needs this Superhero-in-Training.
TL;DR
- The immune system’s job is to protect you from pathogens (any organism that successfully invades the body)
- The immune system is divided into two sections: the innate immune system (non-specific) and the adaptive immune system (specific)
- Key players in your innate immune system are macrophages, mast cells, neutrophils, and dendritic cells
- Cytokines deliver messages from cell to cell and can act as a guide to danger for the innate immune system
- IL-2 is short for interleukin 2 and is a cytokine
- Cancer happens when a cell’s genetic code causes it to clone itself non-stop (without committing controlled cell suicide)
- Cancer cells can form tumors, which can either be benign (stays in one place) or malignant (can move to other parts of the body)
- When malignant tumors go to another segment of the body, it is through a process called metastasis
- Immunotherapy is a medication for cancer that strengthens the immune system
- High Dose (HD) IL-2 is being used in different ways as a form of immunotherapy. It has produced higher response rates 👍 but has many toxicities and restricts immune responses to attack tumors 👎
Additional Resources
https://www.youtube.com/watch?v=fSEFXl2XQpc → This video talks more about the immune system and how it works
https://www.youtube.com/watch?v=jgJKaP0Sj5U → This video shows a Killer T cell attacking a cancer cell 😎
https://www.youtube.com/watch?v=lXfEK8G8CUI → Another video that explains how the immune system works
https://www.youtube.com/watch?v=1AElONvi9WQ → This video explores why blue whales don’t get cancer 😮
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy → This article goes more in-depth on immunotherapy as a whole
https://www.youtube.com/watch?v=s_rQfNTZ5m0 → My own video that goes hand-in-hand with this article!
Works Cited
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938354/
https://www.penguinrandomhouse.com/books/669586/immune-by-philipp-dettmer/
https://www.frontiersin.org/articles/10.3389/fimmu.2014.00491/full
https://cancer.ca/en/cancer-information/what-is-cancer/lymphatic-system
https://cancer.ca/en/treatments/treatment-types/immunotherapy
https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors
https://www.uspharmacist.com/article/cell-based-immunotherapy-for-cancer-treatment-43162
https://www.healthline.com/health/chemotherapeutic-agent#how-do-they-work
