Role Of The Immune System In Cancer Prevention

Some researchers believe the immune system plays a critical role in preventing tumor development by searching out and destroying newly transformed cells. This process, known as immune surveillance, was first proposed by Ehrlich in 1909, and is supported by the following observations that associate immune depression with increased cancer risk:11,12

• Children with immunodeficiency diseases have increased rates of lymphoma, leukemia, and Hodgkin's disease.

• Approximately 40 percent of patients with immuno-suppression caused by the human immunodeficiency virus (HIV) are likely to develop cancer. Common cancers include Kaposi's sarcoma, non-Hodgkin's lymphoma, cervical cancer, and Hodgkin's disease.

• In organ transplant patients who receive immuno-suppressive drugs, the incidence of malignancies is increased about 3-fold. In some studies on kidney transplant patients, the incidence of cancer has been observed to be 7-fold higher than in the general population. Commonly, these malignancies include Kaposi's sarcoma, non-Hodgkin's lymphoma, sarcoma, and cancers of the skin, kidney, cervix, and liver.

• Cancer risk increases with the duration of immuno-suppressive treatment. In a study of heart transplant patients, cancer incidence increased 3-fold after one year of immunosuppressive treatment and 26-fold after five years. In some patients, regression of Kaposi's sarcoma and lymphoma was observed after immunosuppressive therapy ceased.

• Patients with autoimmune diseases treated with im-munosuppressive therapy show increased incidence of acute leukemia, lymphoma, liver cancer, bladder cancer, and skin cancer.

Immunosuppressed patients appear to have a disproportionately high incidence of certain malignancies, such as skin cancers, Kaposi's sarcoma, lymphoma, and acute leukemia. Relatively few of the more common malignancies like breast and lung cancer are seen. This difference may be due to the longer latency period (15 to 20 years or more) of those tumors less apt to develop. Immunosuppressed patients may simply succumb to faster-developing tumors, or infections, before other slow-growing tumors can develop.

An alternate and more likely explanation for this disproportion is that cancers commonly associated with immunosuppressed states are virally induced, or they originate in the immune system itself. Accordingly, the problem is that the immune system fails to destroy viruses that cause or assist the development of cancer rather than that it fails to destroy tumor cells. In some cases, viruses can interfere with the p53 tumor suppressor gene or can activate oncogenes. A number of human viruses are associated with increased risk of cancer. These include the Epstein-Barr virus (EBV), which has been associated with nasopharyngeal cancer and various lymphomas and leukemias. They also include human T-cell leukemia virus type I (HTLV-I), hepatitis B virus (HBV), human papilloma virus (HPV), and several herpes viruses (herpes virus 2, 6, 8, and 16), which have been associated with adult T-cell leukemia, liver cancer, cervical cancer, oral squamous cell carcinoma, naso-pharyngeal cancer, Kaposi's sarcoma, multiple myeloma, lymphoma, Hodgkin's disease, oral squamous cell carcinoma, or penile cancer.13-19

Tumors of viral origin are sometimes referred to as "opportunistic" tumors, in reference to the "opportunistic infections" of immunosuppressed individuals. For example, the short induction time of Kaposi's sarcoma and lymphoma in immunosuppressed patients may reflect a virally induced opportunistic tumor. In organ transplant patients, whose immune systems are purposefully suppressed by drugs to avoid organ rejection, Ka-posi's sarcoma appears, on average, within 20 months of transplant, and lymphoma appears, on average, within 34 months. This is in contrast to the 10- to 20-year period during which most solid tumors develop.

The immune system, then, may play a role in cancer prevention by destroying cancer cells soon after they arise or by destroying viruses that lead to cancer or both. It stands to reason that maintaining a healthy immune system will help prevent cancer.

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