Distribution of tumor-sensitized cells during the induction of permanent tumor regression by chemoimmunotherapy: the use of glucose phosphate isomerase as a marker.
Using a previously described tumor model system, in which permanent tumor eradication was induced by treatment with cyclophosphamide (CY) and adoptively transferred tumor-sensitized (immune) spleen cells, we determined the distribution of the transferred cells in recipient mice. The experiments were carried out using the C57BL/6J (B6) sarcoma, MCA/76-9, and B6 and congeneic B6.CAST.Gpi-Ia strains, which are homozygous for the glucose phosphate isomerase (Gpi) alleles Ib and Ia respectively. Thus, tumor-bearing mice of the one strain were injected with CY (200 mg/kg) 10 days after implantation of tumor cells and 4 h later with an intravenous injection of 50 X 10(6) immune cells from presensitized mice of the other strain. It was observed that the donor-type isozyme was expressed in the tumor within 24 h of injection and continuously up to the time at which the tumor mass had totally regressed (11 days). The tumor-associated macrophage and neutrophil fractions were shown to express host-type isozyme, while the lymphocyte fraction expressed isozyme of both host and donor type. The donor-type isozyme did not appear in the blood until day 4 but persisted thereafter for long periods. The spleen and lymph nodes expressed donor-type isozyme by 1 day after chemoimmunotherapy and remained positive for the duration of the experiments. The adoptive transfer of normal (non-immune) spleen cells gave similar results, except that donor-type isozyme did not persist at the tumor site. The conclusion reached was that the injection of either normal or immune donor spleen cells after CY treatment of B6 mice gave rise to chimeric mice, in which the distribution of normal and immune donor cells was basically similar in terms of overall isozyme expression. However, only immune donor cells resulted in the appearance of both donor and host T cells at the tumor site, suggesting amplification of both donor and host lymphocyte function either at the tumor site or in the lymphoid tissues.
D000483:Alleles; D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005956:Glucose-6-Phosphate Isomerase / Q000032:analysis* / Q000235:genetics; D007116:Immunization, Passive / Q000379:methods; D008198:Lymph Nodes / Q000201:enzymology / Q000276:immunology; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000201:enzymology / Q000276:immunology; D013997:Time Factors
D008748:Methylcholanthrene; D003520:Cyclophosphamide; D005956:Glucose-6-Phosphate Isomerase