EFFECT OF CISPLATIN UPON EXPRESSION OF INVIVO IMMUNE TUMOR RESISTANCE
EFFECT OF CISPLATIN UPON EXPRESSION OF INVIVO IMMUNE TUMOR RESISTANCE
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DOI：
10.1007/bf01789126
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发表时间：
1993-01-01
影响因子：
5.8
通讯作者：
CRUM, ED
中科院分区：
文献类型：
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作者：
CRUM, ED
用细胞毒性药物治疗癌症的主要目的是直接损伤肿瘤细胞，但这些药物中的一些已被证明是免疫调节的。顺铂是一种广泛使用的细胞毒性药物，在最近的临床试验中已与生物反应调节剂联合使用。为了进一步评估顺铂是否可以独立地改变宿主对肿瘤生长的抗性水平，在Mc7肉瘤大鼠肿瘤模型中测试了该药物。在同系Wistar大鼠中，抗Mc7肉瘤的体内肿瘤抗性的表达由循环非细胞毒性T淋巴细胞介导。这些细胞与肿瘤细胞特异性相互作用，在肿瘤攻击部位局部产生细胞毒性效应物。低剂量顺铂（0.3 mg/kg）增加了介导肿瘤抗性的循环淋巴细胞的活性，而高剂量顺铂（9 mg/kg）抑制了介导淋巴细胞活性和抗肿瘤效应机制的产生。这些研究表明，低剂量顺铂可能具有免疫调节作用，将其与生物反应调节剂结合可能是一种有用的策略。然而，高剂量顺铂与生物反应调节剂一起使用可能会抵消这些药物的潜在免疫调节活性。
The major intent of cancer treatment with cytotoxic drugs is direct tumor cell damage, but some of these drugs have been shown to be immunomodulatory. Cisplatin is a widely used cytotoxic drug that has been combined with biological response modifiers in recent clinical trials. To evaluate further whether cisplatin may independently alter the level of host resistance against tumor growth, the drug was tested in the Mc7 sarcoma rat tumor model. The expression of in vivo tumor resistance against Mc7 sarcoma in syngeneic Wistar rats is mediated by circulating non-cytotoxic T lymphocytes. These cells interact specifically with tumor cells to generate cytotoxic effectors locally at the site of a tumor challenge. Activities of these components of expression of tumor resistance were measured in vivo after administration of cisplatin and dose-dependent effects were found. Low-dose cisplatin (0.3 mg/kg) increased the activity of the circulating lymphocytes that mediate tumor resistance, and high-dose cisplatin (9 mg/kg) suppressed both mediator lymphocyte activity and the generation of antitumor effector mechanisms. These studies suggest that low-dose cisplatin may be immunomodulatory and combining it with biological response modifiers might be a useful strategy. However, high-dose cisplatin given with biological response modifiers may negate potential immunomodulatory activities of such agents.