The Immune System and Cancer
Evidence showing the role of the immune system in detecting and killing cancer cells has been available for some time (Richardson MA et al 1999; Wiemann B et al 1994; Hellstrom IE et al 1968; Oliver RT et al 1989; Penn I 1986, 1988; Vose BM et al 1985). This knowledge has been used in developing immunotherapies to bolster the immune system’s natural capacity to counteract cancer cells.
How Does the Immune System Detect Cancer Cells?
Cancer cells display abnormal proteins (antigens) on their surface, and the immune system can detect and destroy cancer cells because of these proteins (Knuth A et al 1991; Naftzger C et al 1991). (An antigen is a substance that causes the immune system to make a specific immune response.)
The immune system has an innate ability to resist cancer development; however, in most cases, the immune system fails due to a series of sophisticated strategies that tumor cells use to evade immune detection. These strategies range from methods designed to hide tumor cells, to active incapacitation of immune cells by tumor-produced agents that lower the immune system’s responses, which are known as immunosuppressive agents (Cordon-Cardo C et al 1991; Junker U et al 1996; Pantel K et al 1991; Ranges GE et al 1987; Sarris AH et al 1999; Staveley-O'Carroll K et al 1998). Therefore, a prerequisite to successful cancer immunotherapy is the implementation of strategies to boost the immune system’s natural resistance to cancer.
T cells and B cells (lymphocytes) are immune system cells responsible for what is known as specific immunity (Brodsky FM et al 1991; Janeway CA, Jr et al. 1994; Levine TP et al 1991). By contrast, other immune cells (for example, eosinophils, natural killer (NK) cells, and macrophages) generate non-specific responses to infections by bacteria and parasites (Klein E et al 1993; Mantovani A et al 1992). T cells and B cells respond only when they detect specific markers that identify infected cells (Brodsky FM et al 1991; Janeway CA, Jr et al. 1994; Levine TP et al 1991).
A Role for the Immune System in Cancer Control
The role of the immune system in counteracting the development of cancer was initially supported by individual clinical case reports. Groundbreaking work in the late 1800s by a New York surgeon, William Coley, noted that some cancer patients who were simultaneously suffering from bacterial infections had regression of their tumors (Richardson MA et al 1999; Wiemann B et al 1994). He concluded that, in trying to fight off the bacterial infection, the patients’ immune systems had become highly activated and that this had given them some resistance to the tumor. Coley later concocted a crude vaccine preparation, called “Coley’s toxins,” that was made up of killed bacteria. While some of Coley’s patients enjoyed complete tumor regression, the responses were somewhat varied and his work was initially regarded with skepticism (Richardson MA et al 1999; Wiemann B et al 1994).
However, more recent research has produced a considerable body of scientific evidence documenting the immune system’s role in controlling cancer growth. For example, cancer occurs more frequently in individuals with weakened immune systems (Oliver RT et al 1992; Penn I 1986, 1988). In addition, some types of cancer undergo spontaneous regression, again adding weight to the notion that the immune system is naturally able to fight cancer (Oliver RT et al 1989). Furthermore, cancer patients often have specific antibodies (proteins that bind to antigens) circulating in their blood, again demonstrating that the immune system can detect tumor cells and mount a specific response (Hellstrom IE et al 1968) that also involves specific T cells, or T lymphocytes (Itoh K et al 1988; Muul LM et al 1987; Vose BM et al 1985).
Why Do Tumors Escape Immune Detection?
Under normal circumstances, all cells display segments of their proteins on their surface. Upon infection with a viral or bacterial agent, cells display on their surface sample segments from these foreign proteins (Brodsky FM et al 1991; Janeway CA, Jr et al. 1994; Levine TP et al 1991). T cells and B cells patrolling the body for foreign invaders seek and destroy any cells that display these foreign proteins on their surface. These proteins are called antigens, substances that can stimulate a specific immune response or activity.
In cancer, the tumor cell also displays a sample of its abnormal proteins on its surface, which can signal the immune system that it is no longer a normal, healthy cell. These protein segments—either from proteins over-produced in the cancer cell or from viral or bacterial proteins that infected the cell and caused the cancer—act as red flags and attract the attention of T cells and B cells (Wang RF 1999). Tumor cells evade immune detection by failing to display protein segments (antigens) on their surface, thus, in effect, hiding from immune cells (Cordon-Cardo C et al 1991; Pantel K et al 1991).
In aggressive cases, tumor cells can also evade immune detection by producing agents that reduce immune cell activity (Junker U et al 1996; Ranges GE et al 1987; Sarris AH et al 1999; Staveley-O'Carroll K et al 1998). Alternatively, the immune system may not be able to cope with a tumor’s rapid growth if the initial immune response to the tumor is not sufficient to reject or control it completely. Despite the immune system’s natural ability to detect and kill cancer cells, in most circumstances the immune system fails to control tumor growth. The goal of immunotherapy is to specifically target tumor antigens as a means of killing cancer cells (Knuth A et al 1991; Naftzger C et al 1991). Table 1 shows some tumor antigens (substances that stimulate an immune response) that form the basis of cancer vaccines in clinical studies.
Table 1: Tumor antigens form the basis of vaccines in clinical development
Carcinoembryonic antigen (CEA)
Colon, breast, lung, pancreatic
Prostate-specific antigen (PSA)
Human papillomavirus nucleoproteins
What You Have Learned So Far
- The immune system has a natural ability to detect and kill cancer cells; however, tumors that develop in the presence of a competent immune system evolve complex immune-evasion strategies to avoid destruction and removal of the tumor.
- Not all tumors are naturally programmed to alert the immune system and mount an immune response, due to loss or coverage of cell surface antigens.
- The goal of immunotherapy is to produce anti-tumor effects through activation of the patient’s immune system or through patient supplementation with natural substances, and thus to ultimately destroy the cancer.
- Therapeutic cancer vaccines are used to boost the immune system as a way to control established cancer. Preventive cancer vaccines are used to vaccinate people against infectious agents known to cause cancer.
- Surgery is often performed to remove most of the tumor before cancer immunotherapy or vaccination, which should then eliminate any persisting tumor cells that would grow or spread.
- For each individual, immune system status is the key factor that will affect the success of cancer vaccine therapy.
- Cancer patients preparing to undergo immunotherapy should ensure optimal immune system function through adequate nutrition and the use of nutritional supplements.