Suppression of Lymphokine-Activated Killer Cell Cytotoxicity by a Soluble Factor Produced by Squamous Tumors of the Head and Neck

Abstract

Incubation of human peripheral blood lymphocytes (PBL) in the presence of interleukin-2 results in the generation of lymphokine-activated killer (LAK) cells that are highly cytotoxic to a variety of autologous and allogenic tumor targets. We have identified a noncytotoxic, soluble factor, produced by human squamous cell cancers of the head and neck, that profoundly inhibits the generation of LAK cytotoxicity. Inhibition of the generation of cytotoxicity was demonstrated with coculture of PBL and freshly disaggregated tumor cells in a Transwell two-chamber system. Alternatively, Inhibition occurred when LAK cells were generated in the presence of tumor-conditioned supernatants alone. These effects were not observed with conditioned supernatants from autologous or allogenic lymphocytes, human fibroblasts, or the erythroleukemia cell line K562. The presence of this inhibitory factor(s) was not required during the entire period of LAK generation. Suppression of cytotoxicity, measured after 4 days of LAK generation, could also be demonstrated when the conditioned tumor supernatant was present in only the last 24 hours of incubation. Suppression is mediated by a heat-labile factor with a molecular weight of >75 kd. These results suggest that LAK cytotoxicity may be significantly impaired by soluble immunoregulatory factors present within the tumor milieu of squamous cell carcinomas of the head and neck. Further characterization of these factors may lead to the development of more rational and effective forms of immunotherapy.