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Radioisotope assay for evaluation of in vivo natural cell‐mediated resistance of mice to local transplantation of tumor cells
Author(s) -
Gorelik E.,
Herberman R. B.
Publication year - 1981
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910270519
Subject(s) - in vivo , spleen , transplantation , adoptive cell transfer , in vitro , biology , microbiology and biotechnology , cell , immunology , cancer research , immune system , t cell , medicine , biochemistry
A radioisotopic assay based on the rate of elimination of [ 125 I]dUrd‐labelled tumor cells from the local site of inoculation was used to study anti‐tumor natural cellmediated immunity in vivo . [ 125 I]dUrd‐labelled YAC‐I, RL♂ I, and M109 tumor cells were inoculated into the footpads of mice and the radioactivity remaining at the site was measured at various times. This method allowed quantitation, in individual mice, of the actual number of tumor cells inoculated and their local clearance. It was found that 90–99% of inoculated YAC‐I or RL♂ I cells were eliminated in the first 24–48 h following transplantation. Participation of NK cells in the local elimination of the transplanted tumor cells was supported by the following findings: (1) The rate of elimination of NK‐sensitive tumor cells was higher than that of the NK‐resistant M 109 tumor cells. (2) There was a positive correlation between the level of in vitro spleen‐cell NK activity of the different strains of mice and the rate of in vivo elimination of YAC‐I. (3) Inoculation of poly I:C or cyclophosphamide increased or decreased, respectively, the clearance of tumor cells in vivo . (4) Local adoptive transfer of normal spleen cells accelerated the rate of tumor cell elimination in vivo . (5) This adoptive transfer of the cytotoxicity was mediated by non‐adherent, non‐T cells that expressed asialo GMI. Despite these correlations between NK activity and the in vivo assay, two major discrepancies were found: YAC‐I cells were eliminated at the same rate in young and old mice, and beige mice were as effective for in vivo clearance of tumor cells as were normal C57BL/6 mice. These data suggested that other natural effector cells may participate in the in vivo destruction of the transplanted tumor cells or that different regulatory processes may operate in vivo . Our findings provide further evidence that natural cell‐mediated immunity can play an important role in the in vivo elimination of the transplanted tumor cells and indicate that this can occur at the local site of tumor inoculation as well as in the lungs or other organs.