It was not always clear to scientists that the immune system played a role in preventing and combating cancer. This idea was proposed in 1957, but the scientific evidence at the time only seemed to indicate that the immune system protected against pathogens like viruses and bacteria, but not against abnormal body cells like cancer cells. Researchers and doctors in the late 1900s noticed, however, that people with extremely weak or no immune system had a greater risk of developing cancer than the average person. In addition, researchers have since noticed that patients with immune cells present in their tumors have a better prognosis than patients without immune cells in their tumors. 1
Immunosurveillance is a term used to describe the action of the immune cells, including T cells, as they move through the body and look for any abnormalities. When cells become mutated, they may appear to the immune cells as abnormal. The body then recognizes them as non-self or foreign. By eliminating cells that have become abnormal, the immune system helps to protect against cancer. However, if the cells mutate enough so that they are able to escape the surveillance mechanisms of the immune system, they may continue to reproduce as cancer cells. The process is a complex version of 'hide and seek' with major consequences.
As described in the previous pages, T cells recognize peptide antigens 'presented' on their cell surface. If pre-cancerous cells present abnormal proteins T cells will recognize these cells as abnormal. Conversely, pre-cancerous cells that the immune system does not recognize as abnormal, or is unable to kill, will survive and may proliferate to form a tumor.
There are many ways that tumor cells may use to get around the immune defenses of the body. Many cancers produce chemical messengers that inhibit the actions of immune cells. Other cancers have defects in the way that antigens are presented on their cell surface. Other immune cells, called natural killer (NK) cells, play a special role in this case, however, because they notice when body cells no longer have present specific 'self' proteins on their surface and kill the abnormal cells. Additionally, some tumors grow in locations such as the eyes or brain, which are not regularly patrolled by immune cells. 2
The main goal of immunotherapy and cancer vaccines is to provide the immune system with the signals that it needs to recognize the cancer cells as abnormal. If successful, these strategies may allow the body to recognize and destroy cancer cells, even those that have been able to form a tumor.
The immune system and the development of cancer.
In addition to fighting cancer, the immune system appears to be actively involved in the development of most, if not all, cancers. A unifying feature is long term inflammation. Inflammation is what happens when immune cells secrete chemicals and proteins in response to a 'threat'. The threat can be an invading microbe (bacteria/virus) or is can be much more subtle. We now know that obesity and stress can both trigger an inflammatory response from the immune system. The inflammation can last for a long time, often for many years. It is the long term activity that causes problems for normal cells, and can lead to the development of cancer.
The inflammation seen in cancer is a good response that has gone bad. There are several different kinds of immune cells that are involved, some of which are discussed below. The inflammation seen in cancer is actively being studied as a possible cancer prevention and cancer treatment target.
Macrophages and tissue remodeling
Macrophages are white blood cells responsible for destroying microbes and foreign material. As macrophages flood the area around a tumor, they become part of a complex tumor microenvironment. Macrophages surrounding the tumor are referred to as tumor associated macrophages (TAMs), and often play a role in tumor growth instead of tumor destruction. The presence of macrophages leads to inflammation, which promotes proliferation of the cancer cells, blood vessel growth, cancer cell invasion, spread to distant locations (metastasis), and resistance to cancer treatments, including chemotherapy.
Circulating monocytes (precursors to macrophages) also play a role in the tumor microenvironment. Inflammatory monocytes (IMs), which usually attack microbes, can be harmful because they promote inflammation, and produce proteins that stimulate inflammation, including tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). Resident monocytes (RMs) normally respond to viruses, and are involved in tissue remodeling, angiogenesis and collagen production. IMs in particular are associated with many cancers.
The way a macrophage acts in the tumor microenvironment can vary. Macrophages that are NOT assisting the growth of the tumor are classified as M1, and those macrophages that are producing products that assist the tumor growth are called M2 macrophages. What induces the change from M1-M2 is currently unknown. Typically, macrophages surrounding a newly developing tumor are M1, and are still working normally to attack the tumor. As the tumor progresses, however, more M2 macrophages are present, promoting pro-tumor activities such as angiogenesis and metastasis. TAMs can also promote local immunosuppression, and as a result, prevent other immune cells from attacking the tumor.34
Bone Marrow Derived Suppressor Cells (Myeloid-derived suppressor cells)
Suppressor cells are immune cells that can block the immune system. In a normally functioning system, we need these cells to reduce or stop the activity of the immune system once a threat has been eliminated. They work to suppress T-cell responses and regulate the production of signaling proteins (cytokines) by macrophages. In cancer and other illnesses, these cells are not acting the way they should, and they can block immune responses against cancer cells.56
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