Inhibition of effector cell functions in natural killer cell activity (NK) and antibody-dependent cellular cytotoxicity (ADCC) in mice by normal and cancer sera.

Abstract

AbstractEffector cells mediating natural killer (NK) cell activity and antibody‐dependent cellular cytotoxicity (ADCC) have been receiving considerable interest recently as they may represent an additional cellular defense mechanism against maglinancy. Spleen cells from normal young C3H (MTV+) female mice were found to have relatively high natural killer (NK) activities toward RL 1 and YAC‐1 tumor cell lines and high antibody‐dependent cell‐mediated cytotoxicity (ADCC) activities toward chicken RBC and SB tumor targets. Serum inhibition of NK and ADCC activities was either not demonstrable or only seen at low levels in the young mice. Following injection of a transplantable mammary adenocarcinoma that grew progressively in these mice, both NK and ADCC activities decreased and serummediated inhibition of both NK and ADCC increased as the tumors grew. NK and ADCC activities declined with age in C3H (MTV+) mice, and the serum inhibition of NK and ADCC activities of young mice increased with age. Aging mice, however, which had developed spontaneous mammary adenocarcinoma, although having increased levels of inhibitor against both NK and ADCC activities and decreased NK and ADCC activities of their spleen cells as compared to young normal mice, did not have different levels from those of aging mice which had not developed the mammary tumor. Correlation was poor between the amount of serum inhibitor(s) on NK and ADCC activities. NK versus RL 1 and ADCC for chicken RBC were not correlated, but NK versus YAC‐1 and ADCC for the tumor cell line SB appeared to be correlated. Decreasing NK and ADCC and increasing serum inhibitory activity toward these functions appeared to correlate with tumor progression. Sera from transplantable tumor‐bearing young C3H mice contained increased amounts of circulating immune complexes, but the amount of circulating immune complexes was only weakly correlated with the serum inhibition of NK activity of spleen cells from young animals by sera from tumor‐bearing young mice. These findings indicate that a serum blocking factor(s) that can inhibit natural cell‐mediated cytotoxicity or antibody‐mediated cytotoxicity in vitro must be considered in analyzing host resistance to tumor growth.