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 [125l]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 51Cr 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.

Down-Regulation of HLA-A Expression Correlates with a Better Prognosis in Colorectal Cancer Patients

“…Laboratory Investigation • December 2002 • Volume 82 • Number 12 supports the antitumor effects of NK cells in animal models (Barlozzari et al, 1985;Gorelik et al, 1982) and in humans (Coca et al, 1997;Riccardi et al, 1980;Tartter et al, 1987;van Duinen et al, 1988;Whiteside and Herberman, 1994). For instance, Blom et al (1997) demonstrated that down-regulation of HLA-A expres- …”

Cellular heterogeneity in a tissue culture cell line derived from a human bladder carcinoma

“…It may be that the 3E clone represents a non-tumorigenic subpopulation within the EJ line, or alternatively the 3E clone induced a host immune response. Although the nude mice lack functional T cells, they do have natural killer (NK) and natural-cytotoxic (NC) cells, which are capable of immumnological surveillance (Herberman, 1980;Riccardi et al, 1980;Warner et al, 1977). As the 3E clone was found to produce tumour nodules in immunodeficient hosts, some of which then regressed, the possibility that the 3E clone elicits a natural immune response from the host is currently being investigated.…”

NK cell-based immunotherapy for malignant diseases

“…NK CELL-MEDIATED ANTITUMOR MECHANISMS NK cells originally described as large granular lymphocytes, exhibited natural cytotoxicity against certain tumor cells in the absence of preimmunization or stimulation. [35][36][37] CD56 dim NK cells, which make up the majority of circulating cells, are the most potent cytotoxic NK cells against tumor cells. Evidence gathered from a mouse xenograft tumor model testing functionally deficient NK cells or antibody-mediated NK cell depletion supports that NK cells can eradicate tumor cells.…”