Saving the best for last. That’s what I tell myself, but really time got away from me and the end of the year is here. I could not let this year end without finishing out the series on the Hallmarks of Cancer. You can read about 1-9 here:
- Sustained proliferative signaling
- Evading growth suppressors
- Resisting cell death
- Enabling replicative immortality
- Inducing angiogenesis
- Activating invasion and metastasis
- Genome instability and mutation
- Tumor promoting inflammation
- Deregulating cellular energetics
The final Hallmark of Cancer is called “Avoiding immune destruction”.
So what is up with the immune system and cancer? Unless you’ve been living under a rock for the last several years, you should know that SOMETHING is up! The immune system is a highly complex biologic system that is composed of many organs, cell types, and processes that protect the entire organism (i.e. the human) against foreign invaders. The immune surveillance theory as it relates to cancer was put forward as early as 1960. This theory (which is now supported by evidence) states that the immune system can detect and destroy tumor cells.
The validity of this theory is confirmed through ‘natural history’ observations. People with immune deficiencies, such as HIV or those on immune suppressants, have a dramatic increased risk of developing certain cancers.
So clearly, if the immune system is destroying some cancer cells and people with an abnormal immune system get more cancers, then the cancers that develop in people with normal immune systems have found a way to go undetected by the immune system.
How do tumors hide from the immune system? This is a BIG area of study and we will undoubtedly learn much more in the upcoming years. We do know that tumor cells reduce the number of sugar and proteins on their surface that are the normal signals that the immune system responds to (mainly the MHC complexes).
As if avoiding the immune system wasn’t enough, we also know that tumor cells will release signals that actually suppress the immune system so that it is less effective. Sneaky, right?
The good news about all of this immune trickery is that we are learning how to use it to fight back against tumors. There were many stories in 2018 about new ‘immunotherapy’ options being developed and approved for cancer drugs.
One type of immune therapy that is hot news is called CAR T cell therapy. Essentially this therapy takes a patients own T cells (immune cells) out via a blood draw and teaches them how to recognize cancer via manipulation in the lab. They are given back to the patient and the T cells go and attack the tumor. This seems like the holy grail right? Well…sort of. These types of therapies have had good success in ‘liquid’ cancers like leukemia, but have fallen short in solid tumors like bone cancers. Kymirah or tisagenlecleucel is the first FDA approved therapy that included a gene therapy step.
The other caveat is that these types of therapies work best when there is only a small amount of disease. If there is too much disease burden, it overpowers the ability of the T cells to clean it up effectively. There is definite hope and excitement that we will improve upon current T cell strategies and they will be viable options for more cancers in the future.
Another type of immunotherapy is using medications to release the ‘brakes’ on the immune system. Like everything in the human body, there is a system of checks and balances. The immune system has to be checked and have brake systems because an out of control or overactive immune system results in disease. This is how auto-immune diseases develop – the immune system starts attacking things that are ‘self’ and not ‘foreign’.
The 2018 Nobel Prize in Medicine was awarded to Drs. Allison and Honjo for their work in developing immune checkpoint inhibitors. These drugs release the brakes on the immune system and allow the body to more effectively recognize tumor cells. This type of therapy has been very successful for cancers such as melanoma. The side effects of these types of drugs are as expected – a fair number of patients develop autoimmune types of issues such as inflammation of the colon, lungs, heart etc. Nothing is without side effects!
There are several other types of immunotherapy that I won’t touch on here – but just know that ‘immunotherapy’ is a bucket term and there are multiple types of therapies included in it.
There you have it – the Hallmarks of Cancer and the 2018 rounded out. Although I would have loved to write more here, life continues to march on and I ended up doing more short snippets and links on my Facebook page and encourage you to follow along if you are interested.
Thanks for sticking with me!
