Effects of cyclosporin A on progressive and regressive tumors induced by two cancer lines derived from a single colon carcinoma chemically induced in the rat.
The effects of cyclosporin-induced immunosuppression were assessed in a rat model of progressive and regressive colonic tumors. Two cloned cell variants, obtained from the same chemically induced colonic carcinoma, differ in their capacity to grow when injected into the syngeneic rat. PROb cells yield progressive tumors and often metastases; in contrast, REGb cells produce tumors which regress in 3 to 6 weeks. Cyclosporin A (CsA) administered daily, 20 mg/kg subcutaneously (s.c.) for 30 days after tumor cell inoculation, drastically enhanced the local growth of PROb tumors and increased the number of metastases. It increased the local growth and prevented the regression of REGb tumors which persisted even as long as 8 weeks after the termination of CsA administration and occasionally yielded metastases. CsA prevented the accumulation of inflammatory cells with the T lymphocyte phenotype at the periphery of both PROb and REGb tumors but did not alter the tumor infiltration by macrophages and NK cells. CsA did not modify the natural cytotoxicity of peripheral blood mononuclear cells against PROb and REGb target cells. These results suggest that CsA-induced suppression of T lymphocyte activity may enhance tumor progression and suppress tumor regression in this model.
Shimizu
T
T
Research Group on Digestive Tumors, INSERM U.252, Faculty of Medicine, University of Dijon, France.
Martin
M S
MS
Pelletier
H
H
Lagadec
P
P
Martin
F
F
D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D009362:Neoplasm Metastasis; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D003524:Cyclosporins