The Immune System
The immune system protects our body from infection. Everyone has had a cold (caused by viruses) and most of us have had an infection for which we took antibiotics. You never get the same cold twice because the immune system remembers, this is also the basis of vaccines. Most vaccines give you a weak form of a virus that will cause immunity without an infection or parts of the virus / bacteria that will allow the body to recognize and fight an infection before it becomes a problem.
The immune system can recognize some cancers. In this section you will learn some basics about the immune system and about how the immune system can (possibly) be used to fight cancer.
The picture to your right shows a tumor cell disintegrating after an attack by a T cell. Two additional, intact tumor cells are shown in. The successful cytotoxic T lymphocyte may now make these cells its targets.
The Immune System Basics
Our immune system protects our body from infection. The immune system is composed of specialized cells that recognize any threatening attack from foreign invaders such as bacteria or viruses. Some medical conditions in which people do not have a normal immune system can predispose them to increased risk of certain infections. Examples of this include some inherited immune deficiencies and diseases like HIV (AIDS) that attack the immune system. Sickness and death associated with AIDS, for example, is typically the result of an uncontrolled infection. Also, certain medications (such as those used following organ transplant) may cause chronic suppression of the immune system which may be associated with increased risks of infection.
The major protective response mounted by the immune system comes from the white blood cells.
There are two main types of immunity: innate, and adaptive. Innate immunity is the non-specific protection against microbes we get from having intact skin and gut lining, as well as the protection provided by certain white blood cells called "phagocytes". Phagocytes are white blood cells such as granulocytes (or "polys") that destroy bacterial microbes in a non-specific fashion.
The other type of immunity, adaptive immunity, provides more specific immunity against foreign invaders. Adaptive immunity is very specific for distinct molecules and is able to generate memory for those molecules. The effector cells of the adaptive immune response are called lymphocytes.
Lymphocytes provide important protection against potentially pathogenic organisms. There are two types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells). The B cells are responsible for antibody production. Antibody molecules may bind to antigens and cause destruction of bacteria, fungus, and viruses. T cells work in different ways. There are two types of T cells: helper T cells, and cytolytic (killer) T cells, also known as CTL. Helper T cells release cytokines when they confront fragments of immunogenic proteins. These cytokines naturally help boost the immune response.
CTL will directly kill a cell expressing an immunogenic protein. (see graphic)
Thus, T cells help B cells make antibodies, or they can directly kill cells that they recognize to be infected. Infected cells may be identified by the immune system if they contain proteins that can act as antigens. Foreign substances that induce specific immune responses are called antigens. Proteins are important building blocks in all living cells and may sometimes act as antigens. Cells contain many types of proteins, though not all proteins are recognized by the immune system. Each encounter with a foreign antigen stimulates increasingly effective defense mechanisms called memory immunity and is the basis for booster immunization.
The way that T cells recognize and process antigen depends most often on a person's "human leukocyte antigen" (HLA) type. HLA proteins are present on the surface of most cells of the body and serve as identifiers that help lymphocytes distinguish normal from foreign cells. HLA type can be determined through a blood test and is similar to the blood type testing that a person might have before receiving a blood transfusion.
The Immune System Recognizes Cancer
How does the immune system recognize cancer? Although much has been learned about interactions between the immune system and cancer, many questions remain unanswered. We know that in order to fight off colds or flu, our immune system must recognize the foreign proteins (antigens) produced by these infections. The same is true for cancer. Some cancers are capable of inducing a measurable immune response, but this response may not be sufficient to prevent tumor growth. Cancers may grow in spite of a normal immune system for several reasons. One potential reason is that cancers are not very immunogenic, meaning they don’t stimulate immune system recognition despite being composed of abnormal cells. Cancers may also suppress the immune system directly.
We do have clues that vigorous immune responses may be protective against some types of cancer. Evidence comes from studies in both mice and humans using different immune-stimulating chemicals. For example, if antibodies are made to bind to cancer antigens, the tumor may become more recognizable for immune destruction. An example of this is the monoclonal antibody Herceptin(r) (trastuzumab). This is an antibody against HER-2/neu, an antigen present in overabundance in some breast cancers and other tumors. Trastuzumab has been found to be an effective treatment for this kind of breast cancer when used either with chemotherapy or alone. There are several ways in which trastuzumab is thought to work, one of which is by increasing immune recognition. Similarly, T cells can directly recognize an antigen on a tumor cell and may assist in destruction of that cell.
We know that tumor antigens exist. Some cancer cells make abnormal or excessive amounts of protein that can serve as a tumor antigen. One example of tumor antigen used in our studies is HER-2/neu (also known as c-erbB-2).
In the picture to your right, the outer membrane of the tumor cell (right) has been shot full of holes by a protein, perforin, secreted from the cytotoxic cell (left). The tumor target cell has become leaky and an influx of water has made it expand in volume; it has also lost many of its surface villi. In addition, there is a large cavity in the membrane of the tumor target cell.
Immune-Based Treatments for Cancer
There are few cancer treatments that effectively use our immune systems. Cancer is very clever at evading immune recognition and it is difficult for the body to mount an immune response to cancer. Researchers at many institutions continue to work on designing immune-based treatments for cancer in an effort to uncover its vulnerable side.
What is cancer immunotherapy? Cancer immunotherapy is a type of treatment designed to use immune system cells to fight cancer. Immunotherapy can be used alone or in conjunction with other conventional treatments such as surgery, chemotherapy, and radiation. Conventional treatments have had substantial impact in the war on cancer. Scientists searching to improve on these gains have begun focusing on the immune system for other useful ways to treat cancer. Using the immune system’s cells to fight cancer is mostly experimental. There are a few immune-based therapies that are "standard of care" in the treatment of cancer such as using antibodies to fight breast cancer and lymphoma. Those drugs are called Herceptin(r) and Rituxan(r), respectively.
Immune-Based Treatments for Cancer: Cytokine Therapy
Cytokine Therapy. Cytokines are proteins that are produced naturally in our bodies. In general, cytokines help our immune system operate more effectively. One of the most studied cytokines, for example, is interleukin-2 (IL-2). IL-2 helps stimulate the immune system by increasing the number of lymphocytes and activating them to make them more effective. Groups worldwide are investigating the use of different cytokines as cancer therapies. Cytokines are also being studied as agents to assist vaccines in being recognized by the immune system (vaccine adjuvants).