MODULATION OF NATURAL-KILLER-CELL FUNCTION LEADING TO SPONTANEOUS REGRESSION OF A HISTIOCYTOMA

AK-5 is a spontaneously regressing rat histiocytoma and the tumor regr ession is mediated by CD8(+) NK cells. We have investigated the functi onal status of effector cells mediating complete remission of the tumo r. The effector-target interaction takes place with the help of antibo dy to AK-5 and the mechanism of lysis involves ADCC. The immune lympho cytes displayed higher ADCC against AK-5 and spontaneous NK activity a gainst YACl targets when compared with normal lymphocytes. Our observa tions demonstrate a direct correlation between antitumor antibody resp onse and the activation of NK cell function in tumor-rejecting animals . The cold target inhibition,assay indicated that both the ADCC and sp ontaneous NK activities were expressed by an identical or overlapping clonotype. The tumor-infiltrating lymphocytes were effective in kiltin g the tumor by ADCC, while the freshly isolated TILs from actively reg ressing tumors exhibited reduced in vitro cytotoxicity. Exposure of im mune splenocytes to AK-5 or YACl cells in vitro resulted in the concom itant loss of ADCC as well as spontaneous NK activity, indicating that both the activities are expressed by common lytic pathway and the ina ctivation of TILs may be due to target-directed exocytosis of NK lytic factors. Based on these results, we propose that the spontaneous regr ession of AK-5 tumor is achieved by direct lysis of antibody-tagged AK -5 cells by tumor-infiltrating NK cells and the intrinsic ability of t he activation/reactivation of NK cells may restore their effector func tion to participate in the complete regression of the tumor. (C) 1994 Academic Press, Inc.