North R J
J Exp Med. 1982 Apr 1;155(4):1063-74. doi: 10.1084/jem.155.4.1063.
On the basis of preceding studies showing that tumor-induced, T cell-mediated immunosuppression serves as an obstacle to adoptive immunotherapy of the Meth A fibrosarcoma, it was predicted that cyclophosphamide treatment of tumor bearers would remove this obstacle and allow passively transferred immune T cells to cause tumor regression. It was found that infusion of immune spleen cells alone had no effect on tumor growth, and cyclophosphamide alone caused a temporary halt in tumor progression. In contrast, combination therapy consisting of intravenous injection of 100 mg/kg of cyclophosphamide followed 1 h later by intravenous infusion of tumor-immune spleen cells caused small, as well as large tumors, to completely and permanently regress. Tumor regression caused by combination therapy was completely inhibited by intravenous infusion of splenic T cells from donors with established tumors, but not by spleen cells from normal donors. These suppressor T cells were eliminated from the spleen by treating the tumor-bearing donors with 100 mg/kg of cyclophosphamide. Immune T cells, in contrast, were resistant to this dose of cyclophosphamide. These results show that failure of intravenously-infused, tumor-sensitized T cells to cause regression of the Meth A fibrosarcoma growing in its syngeneic or semi-syngeneic host is caused by the presence of a tumor-induced population of cyclophosphamide-sensitive suppressor T cells.
基于先前的研究表明肿瘤诱导的、T细胞介导的免疫抑制是Meth A纤维肉瘤过继性免疫治疗的障碍，预计对荷瘤者进行环磷酰胺治疗将消除这一障碍，并使被动转移的免疫T细胞导致肿瘤消退。结果发现，单独输注免疫脾细胞对肿瘤生长没有影响，单独使用环磷酰胺会使肿瘤进展暂时停止。相比之下，联合治疗包括静脉注射100mg/kg环磷酰胺，1小时后静脉输注肿瘤免疫脾细胞，可使大小肿瘤完全且永久消退。联合治疗引起的肿瘤消退被来自已建立肿瘤的供体的脾T细胞静脉输注完全抑制，但正常供体的脾细胞则无此作用。通过用100mg/kg环磷酰胺治疗荷瘤供体，可从脾中消除这些抑制性T细胞。相比之下，免疫T细胞对该剂量的环磷酰胺具有抗性。这些结果表明，静脉输注的、肿瘤致敏的T细胞未能使在同基因或半同基因宿主中生长的Meth A纤维肉瘤消退，是由于存在肿瘤诱导的对环磷酰胺敏感的抑制性T细胞群体。
