Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells.
Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells.
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发表时间：
1989-04
期刊：
影响因子：
11.2
通讯作者：
Michel Awwad;R. J. North
中科院分区：
文献类型：
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作者：
Michel Awwad;R. J. North
结果表明，它是可能的，使用环磷酰胺（Cy）引起免疫介导的消退的免疫原性，Cy-耐药L5178 Y淋巴瘤在同基因和半同基因小鼠。为了使肿瘤消退，有必要在肿瘤植入前不久或植入后不久给予Cy。然而，无论Cy是在肿瘤植入之前还是之后给予，肿瘤消退直到肿瘤进行性生长10天才开始，此时肿瘤直径为1 cm。肿瘤消退与脾脏中Lyt-2+ T细胞数量增加有关，这些细胞能够被动地将免疫转移给荷瘤受体。这种增强的免疫水平在整个肿瘤消退期间持续存在。相比之下，由对照肿瘤携带者产生的较低水平的伴随免疫在肿瘤生长第12天后衰减。因为Cy的治疗效果可以被来自正常供体小鼠的L3 T4 + T细胞的被动转移抑制，所以很明显Cy的治疗效果是基于其优先破坏L3 T4+抑制性T细胞的能力。这些推定的前体抑制性T细胞在被Cy破坏后4天再生。总之，这些结果代表了抑制性T细胞对免疫原性肿瘤的免疫应答的负调节影响的一个引人注目的例子。
It was shown that it is possible to use cyclophosphamide (Cy) to cause immunologically mediated regression of the immunogenic, Cy-resistant L5178Y lymphoma in syngeneic and semisyngeneic mice. In order to cause tumor regression it was necessary to give Cy shortly before or shortly after tumor implantation. However, regardless of whether Cy was given before or after tumor implantation, tumor regression did not commence until 10 days of progressive tumor growth, by which time the tumor was 1 cm in diameter. Tumor regression was associated with the presence in the spleen of an increased number of Lyt-2+ T-cells capable of passively transferring immunity to tumor-bearing recipients. This augmented level of immunity was sustained throughout the period of tumor regression. In contrast, a lower level of concomitant immunity generated by control tumor bearers decayed after Day 12 of tumor growth. Because the therapeutic effect of Cy could be inhibited by passive transfer of L3T4+ T-cells from normal donor mice it is apparent that the therapeutic effect of Cy is based on its ability to preferentially destroy L3T4+ suppressor T-cells. These putative precursor suppressor T-cells were regenerated 4 days after being destroyed by Cy. Taken together the results represent a striking example of the negative regulatory influence of suppressor T-cells on the immune response to an immunogenic tumor.