The precise roles of cytokines in antitumor responses have not been elucidated. Cytokines can exert antitumor effects by many different direct or indirect activities. It is possible that a single cytokine could increase tumor growth directly by acting as a growth factor while at the same time increasing immune responses directed toward the tumor. The potential of cytokines to increase antitumor immune responses was tested in experimental adoptive immunotherapy by exposing the patient’s peripheral blood cells or tumor-infiltrating lymphocytes to cytokines such as IL-2 in vitro, thus generating activated cells with antitumor effects that can be given back to the patient (104–106). Some cytokines can exert direct antitumor effects. Tumor necrosis factor can induce cell death in sensitive tumor cells.
The effects of cytokines on patients with cancer might be modulated by soluble receptors or blocking factors. For instance, blocking factors for TNF and for lymphotoxin were found in ascitic ﬂuid from patients with ovarian cancer (106). Such factors could inhibit the cytolytic effects of TNF or lymphotoxin and should be taken into account in the design of clinical trials of intraperitoneal infusion of these cytokines.
Cytokines have growth-increasing effects on tumor cells in addition to inducing antitumor effects. They can act as autocrine or paracrine growth factors for human tumor cells, including those of nonlymphoid origin. For instance, IL-6 (which is produced by various types of human tumor cells) can act as a growth factor for human myeloma, Kaposi’s sarcoma, renal carcinoma, and epithelial ovarian cancer cells (77–83).
Cytokines are of great potential value in the treatment of cancer, but because of their multiple— even conﬂicting—biologic effects, a thorough understanding of cytokine biology is essential for their successful use (104–117).
Cell biology is characterized by considerable redundancy and functional overlap, so a defect in one mechanism does not invariably jeopardize the function of the cell. When a sufficient number of abnormalities in structure and function occur, normal cell activity is jeopardized, and uncontrolled cell growth or cell death results. Either end point may result from accumulated genetic mutations over time. Factors are identified that enhance the likelihood of genetic mutations, jeopardize normal cell biology, and may increase the risk of cancer.
high-dose chemotherapy with stem cell support may be at increased risk of developing a variety of solid neoplasms. These examples illustrate the importance of immune function in host surveillance for transformed cells. Another example of altered immune function that may be related to the development of cervical dysplasia is the alteration in mucosal immune function that occurs in women who smoke cigarettes (60). The Langerhans cell population of the cervix is decreased in women who smoke. Langerhans cells are responsible for antigen processing. It is postulated that a reduction in these cells increases the likelihood of successful HPV infection of the cervix.
Diet The role of diet in disease prevention and predisposition is widely recognized but poorly understood (116,121). Dietary fat intake is correlated with the risk of colon and breast cancer. Fiber is considered protective against colon cancer. With respect to the female reproductive system, epidemiologic studies provide conﬂicting results. Deficiencies of folic acid and vitamins A and C were associated with the development of cervical dysplasia and cervical cancer. Considerable research must be performed to clarify the impact of diet on cancer prevention and development.
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