Abstract
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 (S0) and at days 5–7 (S1), days 12–14 (S2) and days 25–28 (S3) 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 S1, S2 and S3, compared to S0, whereas the percentage of Treg cells decreased remarkably on S2. The proportions of Th1, Tc1, CD45RO memory T, NKT cells and the ratio of Tc1 to Tc2 cells increased significantly on S2. IFN-γ secreting CD8+ T cells also increased remarkably on S2, 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.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 30801363) and the Foundation of Shanghai Municipal Education Commission (08YZ43). We are very grateful to all patients who participated in this trial.
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X. Wu and Q. Feng contributed equally to this work and should be considered as co-first authors.
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Wu, X., Feng, QM., Wang, Y. et al. The immunologic aspects in advanced ovarian cancer patients treated with paclitaxel and carboplatin chemotherapy. Cancer Immunol Immunother 59, 279–291 (2010). https://doi.org/10.1007/s00262-009-0749-9
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DOI: https://doi.org/10.1007/s00262-009-0749-9