Cytokine modulation of immune defenses in cervical cancer

Human papilloma viruses (HPV) are major factors in the etiology of cervical cancer. Natural killer (NK) lymphocytes, an important defense against viral diseases, are present in most HPV-associated lesions and cervical intraepithelial neoplasia. HPV positive cervical cancer cells and HPV-immortalized human cervical epithelial cells which possess properties similar to cervical dysplasia, however, are resistant to NK but are sensitive to lymphokine-activated killer (LAK) lymphocyte lysis. Sensitivity can be enhanced by treatment of cervical cells with leukoregulin, a cytokine secreted by lymphocytes. Combination treatment with leukoregulin and a chemotherapeutic drug, e.g. cisplatin, further enhances sensitivity of HPV-infected cells to LAK lymphocyte lysis. In contrast, gamma-interferon treatment of cervical cells can result in decreased sensitivity to LAK lysis illustrating the potential balance cytokines can exert in the immunologic control of cervical cancer.