Tzai T S, Lin J S, Chow N H
Department of Urology, Medical College, National Cheng Kung University, Tainan, Taiwan, Republic of China.
J Surg Res. 1996 Oct;65(2):139-44. doi: 10.1006/jsre.1996.0356.
As a tumor progressively grows, the tumor-bearing host usually is under a tumor-mediated immune suppression status. Although surgical resection of the tumor may immediately eliminate most tumor-induced detrimental influences, perioperatively the antitumor immunity of the host remains temporarily suppressed. The major purpose of this study is to investigate the modulation effect of low-dose cyclophosphamide (CY) on the antitumor immunity of tumor-bearing mice (TBM). Using the C3H/He-MBT-2 murine bladder tumor model, we demonstrate that low-dose CY (100 mg/kg) intraperitoneal injection 2 days before tumor resection can significantly enhance the specific antitumor immunity of the TBM. It consequently suppresses the outgrowth of perioperative rechallenged tumor cells and improves the survival of the animals. Phenotypic analysis of cellular subset of spleen by flow cytometry revealed that low-dose CY, when given to both naive and tumor-bearing mice, causes significant reduction of both absolute number and percentage of cells with CD4-CD8- subset in the spleens of TBM. As a result of a parallel increase in the percentage of both CD4+CD8- and CD4-CD8+ subsets, the CD4+/CD8+ ratio remains unchanged. However, after short-term in vitro culture with IL-2 the percentage of the CD4-CD8- subset and CD4+/CD8+ ratio markedly decreased because of the relatively predominant proliferation of the CD4-CD8+ subset. Evidence from in vitro cytotoxicity assays on panel tumor cells and phenotypic analysis revealed that this enhancement of host antitumor immunity, following low-dose CY pretreatment, may be due to augmenting the activity of NK, LAK, and CD11b+ myeloid/macrophages in addition to cytotoxic T lymphocytes.
随着肿瘤的逐渐生长，荷瘤宿主通常处于肿瘤介导的免疫抑制状态。尽管手术切除肿瘤可能会立即消除大多数肿瘤诱导的有害影响，但在围手术期宿主的抗肿瘤免疫力仍会暂时受到抑制。本研究的主要目的是探讨低剂量环磷酰胺（CY）对荷瘤小鼠（TBM）抗肿瘤免疫力的调节作用。使用C3H/He-MBT-2小鼠膀胱肿瘤模型，我们证明在肿瘤切除前2天腹腔注射低剂量CY（100mg/kg）可显著增强TBM的特异性抗肿瘤免疫力。因此，它抑制了围手术期再次接种的肿瘤细胞的生长，并提高了动物的存活率。通过流式细胞术对脾脏细胞亚群进行表型分析发现，低剂量CY给予未感染和荷瘤小鼠时，会导致TBM脾脏中CD4-CD8-亚群细胞的绝对数量和百分比显著降低。由于CD4+CD8-和CD4-CD8+亚群的百分比同时增加，CD4+/CD8+比值保持不变。然而，在与IL-2进行短期体外培养后，由于CD4-CD8+亚群相对占优势的增殖，CD4-CD8-亚群的百分比和CD4+/CD8+比值显著降低。对一组肿瘤细胞进行的体外细胞毒性试验和表型分析的证据表明，低剂量CY预处理后宿主抗肿瘤免疫力的增强可能是由于除细胞毒性T淋巴细胞外，还增强了NK、LAK和CD11b+髓样/巨噬细胞的活性。
