Shimizu T, Martin M S, Pelletier H, Lagadec P, Martin F
Research Group on Digestive Tumors, INSERM U.252, Faculty of Medicine, University of Dijon, France.
Immunobiology. 1989 Feb;178(4-5):401-15. doi: 10.1016/S0171-2985(89)80062-2.
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.
在大鼠进行性和退行性结肠肿瘤模型中评估了环孢素诱导的免疫抑制作用。从同一化学诱导的结肠癌中获得的两种克隆细胞变体，注射到同基因大鼠体内时，其生长能力有所不同。PROb细胞产生进行性肿瘤并常发生转移；相比之下，REGb细胞产生的肿瘤在3至6周内会消退。在肿瘤细胞接种后，每天皮下注射20mg/kg环孢素A（CsA），持续30天，可显著促进PROb肿瘤的局部生长并增加转移数量。它促进了REGb肿瘤的局部生长并阻止了其消退，即使在停用CsA后长达8周，REGb肿瘤仍持续存在，偶尔还会发生转移。CsA阻止了具有T淋巴细胞表型的炎性细胞在PROb和REGb肿瘤周边的聚集，但未改变巨噬细胞和NK细胞对肿瘤的浸润。CsA未改变外周血单核细胞对PROb和REGb靶细胞的天然细胞毒性。这些结果表明，在该模型中，CsA诱导的T淋巴细胞活性抑制可能会促进肿瘤进展并抑制肿瘤消退。
