In vivo natural reactivity of mice against tumor cells

Abstract

A rapid in vivo clearance of tumor cells was found in normal mice following intravenous inoculation of [125 l]dUrd‐labelled YAC‐1 and RBL‐5 cultured cell lines derived from lymphomas. The ability of mice to eliminate tumor cells from spleen, liver and lungs during the first 4 h, as evaluated by the recovery of radioactivity in these organs, was found to correlate with the level of natural killer (NK) cell reactivity in their spleen and lungs, as measured simultaneously in vitro in a shortterm 51 Cr release assay (CRA). Lower recovery of radioactivity was found in mouse strains with high spontaneous levels of NK activity. The degree of clearance was also found to be age‐dependent and older mice of several strains, whose NK activity had declined to low levels, were less effective in eliminating tumor cells. In vivo treatment with interferon and interferon inducers (poly I:C, pyran copolymer, Corynebacterium parvum, murine sarcoma virus) increased the levels of NK activity in the spleen and lungs and also augmented the in vivo clearance of tumor cells from the lungs and liver. Immunopharmacological treatments with antimacrophage agents (silica, iota‐carrageenan, Seakem‐carrageenan), antineoplastic drugs (dexamethasone, cyclophosphamide, 5‐(3,‐3′dimethyl‐I‐triazeno)‐imidazole‐4‐carboxamide, 4‐amino‐L‐D‐arabinofuranosyl‐2‐(IH)‐pyrimidone, adriamycin) or irradiation (850 R γ‐ray) had comparable effects on both in vitro cytolytic activity and in vivo clearance of tumor cells. When the susceptibility to in vitro and in vivocytotoxicity by several other tumors was examined, the lines with detectable sensitivity to lysis by NK cells were found to be cleared in vivo to a greater degree in a high NK strain (CBA) than in a low NK strain (SJL). In contrast, NK‐resistant lines were cleared at approximately the same rate in both strains. However, the actual levels of in vivo clearance and the degree of difference between the strains for the various NK‐sensitive lines did not correlate well with their relative sensitivities to lysis in vitro. In the various situations in which the in vivo recovery of a particular NK‐sensitive line was studied relative to the levels of NK reactivity in the recipients, the best correlations were seen with clearance from the lungs. In several instances, clearance from the spleen did not correlate well with splenic NK activity. These data indicate that rapid in vivo clearance of radiolabelled NK‐sensitive tumor cell lines is appreciably influenced by levels of NK reactivity, but that other factors are probably also involved.