In order to understand how cancer manages to outsmart the immune system, we could imagine the situation as a cop-robber chase. In 2004, Robert Schreiber, an immunologist and professor of Pathology and Immunology at the University of Washington, proposed a theory of how this happens. Schreiber called this process “cancer immunoediting” and divided it into three stages: Elimination, Equilibrium, and Escape.
The three “es” of cancer cells
The immune system, as an invisible army that continually patrols our body looking for intruders, has the ability to recognize a high percentage of cancer cells as something foreign and eliminate them. This is the process known as the Immune Elimination phase. It seems that our immune system is very good at this stage, or at least at the beginning.
However, some cancer cells manage to survive by evading the internal police. They do not grow uncontrollably, but they are not eliminated either. They are in a state of waiting, accumulating small changes that will help them later. It is the Balance phase. Thus, there appears to be a latency period between the end of the Elimination phase and the beginning of the Escape phase.
Finally, in the Escape phase, the tumor cells have modified their ability to be recognized by the immune system by learning to disguise themselves and camouflage themselves. They develop tricks to evade detection, and that allows them to grow and multiply undisturbed.
They cleverly learn to emit the same “peace signals” that healthy cells generate so that the immune system does not attack them by mistake. These peace signs are known as immune checkpoints, and their function is to put to sleep that army that defends us when we find ourselves in a safe situation. Thus, finally, the tumor cells go unnoticed by the immune system and the tumor manages to grow and increase its aggressiveness. So, what seemed like an effective immune system against cancer turns out to be deceived by the tumor itself, which manipulates it to its advantage to spread rapidly throughout our body.
In short, cancer is not only a disease of uncontrolled cells, but also a constant battle between those cells and our immune system where, sometimes, cancer manages to gain the upper hand.
But the story does not end there. While the tumor struts around in its costume and celebrates its supposed victory, a new player appears on the scene: immunotherapy.
A new weapon of the invisible army
Immunotherapy is a therapeutic technique that harnesses the powerful weapons of the immune system to identify and destroy cancer cells, even those hiding behind clever disguises. It helps the immune system recognize that the disguise they are wearing is nothing more than a ruse, and that their true nature poses a threat that must be eliminated.
Before the 21st century, the main treatments for cancer were surgery, radiotherapy and chemotherapy. But there was a telling moment more than a century ago when scientists noticed something peculiar. They found that some advanced cancers disappeared completely after affected people suffered severe bacterial infections and, consequently, a great activation of the immune system. This raised the question: can the immune system fight cancer?
Immunotherapy was born as an answer to this question and completely revolutionized the way we treat cancer. Instead of targeting just cancer cells, scientists realized they had to consider the entire environment in which tumors grow, what we call the “tumor microenvironment.” In this microenvironment, not only cancer cells coexist, but also a very large repertoire of different cells, among which are those of the immune system.
Unlike traditional chemotherapy, which primarily aims to eliminate rapidly dividing cells, immunotherapy focuses on helping the immune system recognize cancer as foreign and eliminate it in a way that prevents tumor growth and spread.
“It’s here to stay”
“Many mistakes were made in cancer research, we didn’t know enough about the immune system. (…) Immunotherapy is here to stay and will be able to combat many types of cancer.” This is how immunologist James Allison expressed his certainty after receiving the Nobel Prize in Medicine in 2018 together with immunologist Tasuku Honjo.
Immunotherapy treatments are much more specific than other therapeutic alternatives such as the aforementioned chemotherapy, which entails less severe side effects. Furthermore, by boosting the memory of the immune system it allows it to continue recognizing the tumor as “foreign”, thus prolonging its action and offering potential long-term benefits.
And unlike traditional methods, such as radiotherapy or chemotherapy, which are often not curative, immunotherapy offers a different perspective. Once the immune system generates the soldiers that go out and kill the cancer cells, we have them for the rest of our lives. This leads to long survivals for some patients who receive this type of treatment.
However, one may wonder why immunotherapy is not a treatment for all cancer patients.
Hot and cold tumors
Cancer is a group of diverse diseases and, as such, each tumor has its own behavior. Our immune cells are the main allies in the treatment of cancer immunotherapy. In some cases, more than 40% of the tumor may be made up of these defensive cells. It is what is known as a “hot tumor” and seems to respond better to this type of treatment.
On the other hand, there are tumors with few infiltrated immune cells, such as glioblastoma. Known as “cold tumors”, immunotherapy is not as efficient in them. However, strategies are being studied to increase the number of infiltrating defense cells in these tumors and thus improve the effectiveness of the treatment.
In addition, specific characteristics of cancer patients that may be predictive are being investigated to identify which ones will benefit the most from immunotherapy.
“Of course, while there may not be truly curative treatments, there are many therapies that can prolong life, with quality of life, until those new cures appear. There is a lot of science being developed and progress is being made quickly. I would say it is time for optimism. But we have a long way to go, which also requires hard work and needs the support of the public to achieve it,” James Allison confided in another interview.
This article was the winner of the IV edition of the youth outreach contest organized by the Lilly Foundation and The Conversation Spain.
This article was originally published on The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts.
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Candelaria Aguilar García is a recipient of predoctoral support from the Scientific Foundation of the Spanish Association Against Cancer 2022 (PRDAS222516AGUI). This project is funded by the Carlos III Health Institute, Grant/Award Number: PI23/01576.