To understand how cancer manages to outsmart the immune system, we could think of the situation as a policeman chasing a robber. 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.
Three “E”s of Cancer Cells
The immune system, like an invisible army that constantly patrols our body in search of intruders, has the ability to recognize a high percentage of cancer cells as foreign and destroy them. This is a process known as the immune elimination phase. It seems that at this stage, or at least in the beginning, our immune system is very good.
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 anticipation, accumulating small changes that will help them in the future. This is the balance phase. Thus, there is a latency period between the end of the elimination phase and the beginning of the escape phase.
Finally, during the escape stage, tumor cells changed their ability to be recognized by the immune system, learning to camouflage and disguise themselves. They invent tricks to avoid detection, which allows them to grow and reproduce unhindered.
They cleverly learn to emit the same “peace signals” that healthy cells emit, so that the immune system does not attack them by mistake. These peace signs are known as immune checkpoints, and their function is to lull the army that protects us when we find ourselves in a safe situation. Thus, ultimately, tumor cells remain undetected by the immune system, and the tumor has time to grow and become more aggressive. So, what seemed to be an effective immune system against cancer turns out to be deceived by the tumor itself, which manipulates it to its advantage in order to quickly spread 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, in which sometimes cancer manages to gain the upper hand.
But the story doesn’t end there. While the tumor struts around in its suit and celebrates its supposed victory, a new player appears on the scene: immunotherapy.
New weapons of the invisible army
Immunotherapy is a therapeutic approach that uses the immune system’s powerful weapons to identify and destroy cancer cells, even those hiding behind elaborate disguises. This helps the immune system recognize that the disguise they wear is nothing more than a ruse, and that their true nature is a threat that must be eliminated.
Until the 21st century, the mainstays of cancer treatment were surgery, radiation, and chemotherapy. But more than a century ago, there was a landmark moment when scientists noticed something strange. They discovered that some advanced cancers disappeared completely after the people affected suffered severe bacterial infections and, as a result, a significant activation of the immune system. This raised the question: could the immune system fight cancer?
Immunotherapy was born as an answer to this question and has completely revolutionized the way cancer is treated. Instead of targeting just cancer cells, scientists realized that they needed 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, including cells of the immune system.
Unlike traditional chemotherapy, which primarily aims to kill rapidly dividing cells, immunotherapy aims to help the immune system recognize the cancer as foreign and eliminate it in a way that prevents the tumor from growing and spreading.
“It’s here to stay”
“There were a lot of mistakes made in cancer research and we didn’t know enough about the immune system. (…) Immunotherapy is here to stay and will be able to fight many types of cancer.” This is how immunologist James Ellison expressed confidence after receiving the Nobel Prize in Medicine in 2018 along with immunologist Tasuku Honjo.
Immunotherapy is much more specific than other therapeutic alternatives, such as the aforementioned chemotherapy, which carries less severe side effects. Moreover, by improving the immune system’s memory, it allows it to continue to recognize the tumor as “foreign”, thereby prolonging its action and offering potential long-term benefits.
And unlike traditional methods such as radiation therapy or chemotherapy, which are often not curative, immunotherapy offers a different perspective. Once the immune system generates soldiers that go out and kill cancer cells, they stay with us for the rest of our lives. This results in long survival for some patients receiving 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 therefore each tumor has its own behavior. Our immune cells are our greatest allies in treating cancer with immunotherapy. In some cases, more than 40% of the tumor may consist of these protective cells. This is what is called a “hot tumor” and appears to respond better to this type of treatment.
On the other hand, there are tumors with few infiltrated immune cells, such as glioblastoma. Immunotherapy, known as “cold tumors,” is not as effective for them. However, strategies are being explored to increase the number of infiltrating protective cells in these tumors and thus improve treatment efficacy.
In addition, specific characteristics of cancer patients that may be prognostic are being examined to determine which patients will benefit most from immunotherapy.
“Of course, while there are no truly curative treatments, there are many treatments that can prolong life by improving quality of life until new drugs become available. Science is actively developing and progress is being made quickly. I’d say it’s time for optimism. But we have a long way to go, which also requires hard work and public support,” admitted James Ellison in another interview.
This article was the winner of the IV Youth Outreach Competition organised by the Lilly Foundation and The Conversation Spain.