Role of the Immune System - Pathophysiology of the Malignant Process

ROLE OF THE IMMUNE SYSTEM

In humans, malignant cells are capable of developing on a regu-lar basis. Some evidence indicates, however, that the immune sys-tem can detect the development of malignant cells and destroy them before cell growth becomes uncontrolled. When the im-mune system fails to identify and stop the growth of malignant cells, clinical cancer develops.

Patients who for various reasons are immunoincompetent have been shown to have an increased incidence of cancer. Organ transplant recipients who receive immunosuppressive therapy to prevent rejection of the transplanted organ have an increasedincidence of lymphoma, Kaposi’s sarcoma, squamous cell cancer of the skin, and cervical and anogenital cancers. Patients with immunodeficiency diseases, such as AIDS, have an increased in-cidence of Kaposi’s sarcoma, lymphoma, and rectal and head and neck cancers. Some patients who have received alkylating chemotherapeutic agents to treat Hodgkin’s disease have an in-creased incidence of secondary malignancies. Autoimmune dis-eases, such as rheumatoid arthritis and Sjögren’s syndrome, are associated with increased cancer development. Finally, age-related changes, such as declining organ function, increased incidence of chronic diseases, and diminished immunocompetence, may con-tribute to an increased incidence of cancer in older people.

Normal Immune Responses

Normally, an intact immune system has the ability to combat cancer cells in several ways. Usually, the immune system recog-nizes as foreign certain antigens on the cell membranes of many cancer cells. These antigens are known as tumor-associated anti-gens (also called tumor cell antigens) and are capable of stimu-lating both cellular and humoral immune responses.

Along with the macrophages, T lymphocytes, the soldiers of the cellular immune response, are responsible for recognizing tumor-associated antigens. When T lymphocytes recognize tumor antigens, other T lymphocytes that are toxic to the tumor cells are stimulated. These lymphocytes proliferate and are released into the circulation. In addition to possessing cytotoxic (cell-killing) properties, T lymphocytes can stimulate other components of the immune system to rid the body of malignant cells.

Certain lymphokines, which are substances produced by lym-phocytes, are capable of killing or damaging various types of ma-lignant cells. Other lymphokines can mobilize other cells, such as macrophages, that disrupt cancer cells. Interferon (IFN), a sub-stance produced by the body in response to viral infection, also possesses some antitumor properties. Antibodies produced by B lymphocytes, associated with the humoral immune response, also defend the body against malignant cells. These antibodies act either alone or in combination with the complement system or the cellular immune system.

Natural killer (NK) cells are a major component of the body’s defense against cancer. NK cells are a subpopulation of lympho-cytes that act by directly destroying cancer cells or by producing lymphokines and enzymes that assist in cell destruction.

Immune System Failure

How is it, then, that malignant cells can survive and proliferate despite the elaborate immune system defense mechanisms? Sev-eral theories suggest how tumor cells can evade an apparently in-tact immune system. If the body fails to recognize the malignant cell as different from “self ” (non-self or foreign), the immune re-sponse may not be stimulated. When tumors do not possess tumor-associated antigens that label them as foreign, the immune response is not alerted. The failure of the immune system to re-spond promptly to the malignant cells allows the tumor to grow too large to be managed by normal immune mechanisms.

Tumor antigens may combine with the antibodies produced by the immune system and hide or disguise themselves from nor-mal immune defense mechanisms. These tumor antigen–antibody complexes can suppress further production of antibodies. Tu-mors are also capable of changing their appearance or producing substances that impair usual immune responses. These substances not only promote tumor growth but also increase the patient’s susceptibility to infection by various pathogenic organisms. As a result of prolonged contact with a tumor antigen, the patient’s body may be depleted of the specific lymphocytes and no longer able to mount an appropriate immune response.

Abnormal concentrations of host suppressor T lymphocytes may play a role in developing cancers. Suppressor T lymphocytes normally assist in regulating antibody production and diminish-ing immune responses when they are no longer required. Low levels of serum antibodies and high levels of suppressor cells have been found in patients with multiple myeloma, a cancer asso-ciated with hypogammaglobulinemia (low amounts of serum antibodies). Carcinogens, such as viruses and certain chemicals, including chemotherapeutic agents, may weaken the immune system and ultimately enhance tumor growth.