Natural killer cells in human solid tumors

Natural killer (NK) cells have been studied in human neoplastic diseases in an effort to assess the role of these cells in the control of human neoplasia and to monitor the effects of therapeutic regimens expected to affect this reactivity. NK activity measured against susceptible cell lines is usually somewhat depressed in patients bearing advanced solid tumors, but not at early disease stages. Lymphoid cells associated with solid tumor tissues or effusions have usually low NK cytotoxicity, with considerable differences among histologic types (e.g., nasopharyngeal carcinoma versus other tumors) or at different sites involved by the same tumor (e.g., peritoneal effusions versus solid lesions in ovarian carcinoma). The low levels of NK activity of tumor-associated lymphoid cells are primarily related to a low frequency in the relevant effector cells at the tumor site, although suppression of the in vitro maintenance of cytotoxicity by in situ macrophages and lymphocytes has been described in a few patients. Treatment with immunopharmacologic agents, interferons in particular, has been reported to augment NK activity in cancer patients, but it is unclear how blood NK activity relates to tissue levels of this reactivity. Limited evidence indicates that blood NK levels need not be representative of the activity of tumor associated lymphoid cells. Most studies on NK cells in human neoplasia have dealt with reactivity against susceptible tissue culture lines, but freshly isolated human tumors are generally relatively resistant to these effector cells, particularly when autologous lymphoid cells are used. The resistance of fresh human neoplastic cells to NK activity has not been studied extensively and, together with the poor localization at the tumor site of NK effectors, it represents a major difficulty in envisaging a role for these cells in the control of established human neoplasia.