When the immune system is exhausted

Imagine how exhausted we are after finishing a 10k run. We might want to cool down a bit to recover before doing any physical activities again.

But did you know that our immune system can be exhausted too? Yes, they can, and exhaustion is the keyword here. Immune exhaustion is real, and it’s not the same to what we feel after finishing a race.


Exhausted, but not worn out

Immune exhaustion does not mean our immune system is overworked or running out of energy. It means it cannot detect and react to any infectious agents or diseases. In other words, it’s irresponsive.

Should we freak out?

Yes, we should.

Our immune system is our body’s defence force against diseases. When it cannot do its proper work, our body is weaker. Immune exhaustion happens during disease development in our body, such as cancer and AIDS.


Nope, we’re not talking about this kind of exhaustion. Photo by Massimo Sartirana on Unsplash

Smart cancer cells, happy cancer cells

Our immune cells are actually capable of combating cancer cells. One of the immune cells, cytotoxic T cells (Tc cells), can recognise cancer as a threat through an interaction with neoantigen on the surface of cancer cells. This interaction via neoantigen ends with (spoiler alert) cancer cells death.

But, cancer cells are smart. They know how to escape Tc cells radar.

Cancer cells overproduce a surface protein called protein-death ligand 1 (PD-L1). This protein, when binds to its pair called PD-1 on the surface of Tc cells, sends a deactivating signal to the Tc cells.

PD-L1 – PD-1 interaction shuts down cytotoxic T cells activity, making them exhausted and unable to kill cancer cells. Image by Author

Naturally, PD-L1 – PD-1 interaction functions as a stop signal for Tc cells to avoid any autoimmune reaction to our body. Note that almost all cells in our body have PD-L1 on their surface, while cancer cells overproduce it.

However, as Tc cells activity might be harmful for cancer growth, cancer cells send the “brakes signal” as much as they can to Tc cells. Once shut down, Tc cells lose their ability to detect and kill cancer cells. In other words, they are exhausted.

As a result, cancer cells can grow rapidly, happily, and dangerously, without any threat from our body’s immune cells.

Scary isn’t it?


Boosting Immunity by Outsmarting Cancer

The solution of immune exhaustion is to prevent the interaction that causing it at the first place. Blocking the PD-L1 – PD-1 interaction can prevent Tc cells from “hitting the brakes”.  Therefore, this blocking can boost our immune system and promote Tc cells anti-cancer activity.

Scientists have been busy testing new drugs, or what so called immune checkpoint inhibitors, as the blockade. Some drugs are already established and proven to be effective in skin, lung, and renal cancers. This therapy is a type of cancer immunotherapy.

When PD-L1 – PD-1 interaction is blocked by drugs (PD-L1 inhibitor), Tc cells are not exhausted and they regain their anti-cancer capacity! Image by Author


However, it might take a while for scientists to cover other types of cancer. This is due to different conditions in different tissues. For example, brain cancer might be a bit of a challenge due to the Blood-Brain Barrier (I wrote about it on my previous blog!), which causes difficulties in drug delivery to cancer sites.

The good thing is, we know the cure of cancer is in our body. We just need to support it to outsmart the disease.

10 Responses to “When the immune system is exhausted”

  1. Sam Widodo says:

    Thanks for the feedback, Marissa!

  2. Marissa Nalenan says:

    Very well written blog! I feel like I have a better understanding of immunity exhaustion now.

  3. Sam Widodo says:

    Many thanks Daljeet! glad you enjoyed reading this one.

  4. Sam Widodo says:

    Hi Alexander! thanks for reading my blog. Glad that you learnt something from it.

  5. Sam Widodo says:

    Hi Matthew, thanks for the feedback! The term ‘exhaustion’ refers to T cells functional status. However, other immune cells may also contribute to this condition, for example cancer cells can induce macrophage (other types of immune cells) to produce PD-L1, and thus exacerbate the condition.

  6. Sam Widodo says:

    Hi Deb, thanks for reading my blog. Hope you’re getting better from the viral infection. Yes, some types of cancer can be pretty sneaky. I wish your friend a speedy recovery. Thanks for sharing the story.

  7. Daljeet Walia says:

    An interesting blog full of information. The simple and concise way of writing and used images helps to understand the immunity exhaustion in a clear way!!

  8. Alexander says:

    I loved the illustrations you did! Definitely helped with understanding how the TC cell receives a deactivation signal. I’ve never studied immunity and this was very clear and concise! 🙂

  9. Matthew Graham says:

    I found this blog both interesting and informative. I only wonder if ‘exhaustion’ only occurs in T cells specifically? Or can it potentially affect all immune cells?

  10. Deb says:

    Hi I really liked this article, it was well written. For me, this article resonated with me from having a virus that wiped out my immunity. My friend who is in remission her oncologist is always looking at ways to boost her immunity and outsmart the disease. Her onocologist suggest higher than recommended levels of vit D and vit b 12 as part of the suite of recommendations to naturally help keep her well. Interestingly there is a study presently looking at Chinese herbal medicine and accupuncture to help outsmart the return of cancer- it has had some interesting results.