The immunologic aspects in advanced ovarian cancer patients treated with paclitaxel and carboplatin chemotherapy
The immunologic aspects in advanced ovarian cancer patients treated with paclitaxel and carboplatin chemotherapy
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紫杉醇和卡铂化疗晚期卵巢癌患者的免疫学方面
DOI：
10.1007/s00262-009-0749-9
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发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Di, Wen
中科院分区：
文献类型：
--
作者：
Wu, Xia;Feng, Qin-Mei;Di, Wen
到目前为止，关于化疗对癌症患者免疫力的影响以及免疫治疗与化疗联合的理想时机（“窗口”期）知之甚少。在本研究中，我们探讨了紫杉醇和卡铂诱导卵巢癌细胞凋亡的免疫原性，卵巢癌化疗患者的免疫学方面，以及在“窗口期”用肿瘤抗原刺激CD 8（+）T细胞时的CTL应答。首先检测凋亡卵巢癌细胞的免疫原性。然后，在化疗前（S-0）和化疗后第5-7天（S-1）、第12-14天（S-2）和第25-28天（S-3）从每个卵巢癌患者获得血液样品。观察免疫细胞亚群比例及NK细胞功能。我们发现，凋亡的卵巢癌细胞在体外引起了强大的CTL反应与抗肿瘤活性。与S-0相比，S-1、S-2和S-3上的CD 3（+）T细胞、CD 4（+）T细胞比例和CD 4（+）/CD 8（+）细胞比例无显著变化，而S-2上的Treg细胞百分比显著降低。在S-2上，Th 1、Tc 1、CD 45 RO记忆T、NKT细胞比例和Tc 1/Tc 2细胞比例显著增加。分泌IFN-γ的CD 8（+）T细胞在S-2上也显著增加，尤其是当用自体肿瘤抗原刺激CD 8（+）T细胞时。从我们的观点来看，化疗诱导暂时的免疫重建并增强抗肿瘤免疫应答。化疗后12-14天的“窗口”期可能为免疫治疗提供了最佳机会。
Till now, little is known about the effects of chemotherapy on the immunity of cancer patients and the ideal timing ("window" period) for immunotherapy combined with chemotherapy. In this study, we addressed the immunogenicity of apoptotic ovarian cancer cells induced by paclitaxel and carboplatin, the immunologic aspects in ovarian cancer patients under chemotherapy, and the CTL response when CD8(+) T cells were stimulated with tumor antigen in the "window" period. The immunogenicity of apoptotic ovarian cancer cells was detected first. Then, blood samples from each ovarian cancer patient were obtained before (S-0) and at days 5-7 (S-1), days 12-14 (S-2) and days 25-28 (S-3) after chemotherapy. The proportions of immunocyte subsets and the function of NK cells were studied. We found that apoptotic ovarian cancer cells elicited a powerful CTL response with antitumor activity in vitro. The proportions of CD3(+) T cells, CD4(+) T cells and the ratio of CD4(+) to CD8(+) cells did not change significantly on S-1, S-2 and S-3, compared to S-0, whereas the percentage of Treg cells decreased remarkably on S-2. The proportions of Th1, Tc1, CD45RO memory T, NKT cells and the ratio of Tc1 to Tc2 cells increased significantly on S-2. IFN-gamma secreting CD8(+) T cells also increased remarkably on S-2, especially when CD8(+) T cells were stimulated with autologous tumor antigen. From our point of view, chemotherapy induces temporary immune reconstitution and augments anti-tumor immune response. It is probable that the "window" period of days 12-14 after chemotherapy provides the best opportunity for immunotherapy.