Rozková Daniela, Tiserová Hana, Fucíková Jitka, Last'ovicka Jan, Podrazil Michal, Ulcová Hana, Budínský Vít, Prausová Jana, Linke Zdenek, Minárik Ivo, Sedivá Anna, Spísek Radek, Bartůnková Jirina
Institute of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic.
Clin Immunol. 2009 Apr;131(1):1-10. doi: 10.1016/j.clim.2009.01.001. Epub 2009 Feb 8.
Immunotherapy has emerged as another treatment modality in cancer. The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%.
免疫疗法已成为癌症的另一种治疗方式。晚期癌症患者免疫疗法的目标不一定是彻底根除肿瘤细胞，而是恢复肿瘤细胞与免疫反应之间的动态平衡。适当结合肿瘤体积缩小（通过手术和/或化疗）以及中和肿瘤诱导的免疫抑制，可能为通过主动免疫疗法诱导抗肿瘤免疫反应创造合适条件。我们回顾了联合化疗免疫疗法的实验基础和关键概念，并在一例预后凶险的激素难治性转移性前列腺癌患者的病例报告中记录了其原则。四百多名前列腺癌患者接受了基于树突状细胞（DC）的免疫疗法治疗，其中三分之二报告有肿瘤特异性免疫反应。在这些患者中，一半患者的DC免疫疗法产生了短暂的临床反应。调节性T细胞（Tregs）等因素可有效抑制肿瘤特异性T细胞。前列腺癌患者循环和肿瘤浸润的Tregs数量增加，有证据表明Tregs在体内促进肿瘤生长。由于我们患者中循环Tregs的频率较高，我们首先给予小剂量环磷酰胺。获得机构审查委员会（IRB）批准后，我们开始定期用负载有灭活前列腺癌细胞的树突状细胞（DCs）进行疫苗接种。根据联合免疫疗法的原则，我们继续用多西他赛进行姑息化疗以减轻肿瘤细胞负担。基于DC的疫苗接种诱导了前列腺癌细胞特异性免疫反应。由交替疗程的化疗和用LNCap前列腺癌细胞系脉冲处理的成熟DC进行疫苗接种组成的联合化疗免疫疗法，使临床和实验室表现显著改善，前列腺特异性抗原（PSA）水平下降超过90%。
