Cancer Immunology pt. 1: The Trouble with Cancer

by Andrew Wight

Treating cancer used to be all about chemotherapy, radiation, and surgery. While these techniques could be effective, they are dangerous, non-specific, and often don’t address the problem of a cancer relapse. That’s why modern research into new cancer therapies is focusing on using our own immune systems to destroy the cancer. In contrast to these older therapies, the immune system is very specific, having the ability to kill cancer cells while leaving neighboring healthy cells unharmed. Moreover, the immune system has memory—the ability to recognize an enemy it has seen before and kill it even better the second time—and so can defend against relapse and metastasis. In this article series, we will give an overview of the immune system: how it works, and how scientists are trying to use it against cancer. Our hope is that new immune-based therapies will usher in a generation of anti-cancer treatments that are safe, effective, and long-lasting.

So if the immune system is so great, why are we only now using it against cancer? There are two reasons for this. First, immunology—the study of the immune system and its interactions with diseases—is a relatively young field, having only really taken off in the 1950s. We’re only now at a state of knowledge where we can hope to make intelligent decisions about immune therapies. Second, of all the challenges that the immune system faces on a daily basis, cancer may be the most difficult and the most complicated. Today’s article will cover a little bit about what makes cancer so tough for the immune system: the problem of self vs. non-self.

Self/non-self discrimination—the ability for the immune system to identify and distinguish our own cells from those that are invading the body from the outside—is the key for the immune system’s activity. Immune cells use this ability to recognize bacterial cells and cells infected with viruses as ‘non-self’, and then take steps to kill the non-self cells while leaving any nearby ‘self’ cells intact. This self/non-self discrimination is very strictly enforced in the immune system, and with good reason: a breakdown in the ability to distinguish self and non-self cells leads to autoimmune diseases such as multiple sclerosis, arthritis, and type I diabetes. However, this presents a huge difficulty when it comes to cancer. Unlike bacteria and viruses, cancer is a disease where self cells grow uncontrollably, essentially becoming a parasite on the body. However, because they are self cells, the immune system is specifically trained to avoid killing them. Thus, the first challenge in cancer immune therapies is making the immune system able to even recognize the cancer cells as a threat. There are some immune cells, such as the natural killer (NK) cell, that has specifically evolved to deal with this cancer hurdle, and we’ll talk about it in a coming article. Also, extensive work is now underway to develop antibody therapies like Rituximab, which are able to light up a tumor to the immune system. Unfortunately, making the immune system recognize a cancer cell without breaking tolerance to healthy self cells is still a major challenge, and must be overcome if we are ever to achieve the dream of cancer vaccines.

Even if we are able to make the immune system recognize a cancer cell, there is another challenge it must overcome to successfully kill the tumor. As mentioned above, it is possible for the immune system to go haywire, leading to autoimmune diseases. Because of this, our immune systems have evolved something called the regulatory response. The regulatory response is a type of immune response that acts against the conventional immune system, shutting down inflammation and preventing the killing of cells. This regulatory response is important in preventing autoimmune diseases and in cleaning up normal immune responses once their target is dead. Cancer, however, is able to recruit the regulatory response and invoke it to shut down an anti-cancer immune response. Essentially, the cancer sends out a distress cry, claiming to be a self cell and blaming the immune response for starting an autoimmune reaction, and so the regulatory response activates and shuts down the anti-cancer immune response. This regulatory response has proven to be a big problem in the field of cancer immune therapy—again, we need to find a way to block the regulatory response to cancer, while preserving it in other cases to prevent real autoimmune disease. There is some hope, however—recent advances in treatments known as checkpoint inhibitors have been able to relieve some of the regulatory response to cancer, and work here in Ottawa is ongoing to study how to blunt the extremely strong regulatory response that is induced after a cancer surgery.

So now you know what the immune system is up against. Fortunately, as sneaky as cancer can be, the immune system has a number of tricks up its sleeve as well. Tune in next time as we look at the first line of defense against cancer—the innate immune system.