Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer
Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer
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DOI：
10.3892/ijo_00000368
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发表时间：
2009-09-01
影响因子：
5.2
通讯作者：
Lacave, Roger
中科院分区：
文献类型：
--
作者：
Lemoine, Francois M.;Cherai, Mustapha;Lacave, Roger
细胞毒化疗对转移性肾癌无效。然而，全身应用白介素2(IL-2)或输注负载肿瘤提取物的树突状细胞(DC)可以导致一定的应答率，同时伴随着生存的改善。我们报告了一项结合DC和IL-2的I-II期试点研究的结果，其中包括6名患者。DC来源于骨髓CD34(+)细胞，负载自体肿瘤提取物。术后第45、52、59、90和120天分别皮下注射CD34-DC疫苗和IL-2，然后在第3和第4次DC疫苗接种后给药。除一名患者外，肿瘤提取物和CD34-DC的制备对所有患者都是满意的。由于肿瘤进展迅速，一名患者在接种疫苗前被排除在外。在剩下的4名患者中，2名患者接受了3次疫苗接种，另外2名患者接受了5次疫苗接种和完整的IL-2治疗。未观察到接种疫苗的不良反应。在完成治疗的2名患者中，观察到了针对自体肿瘤细胞的特异性免疫反应。有趣的是，这2名患者比接受3次疫苗接种的患者存活时间更长。重要的是，3名患者在接受IL-2治疗后，循环中自然调节性T细胞(NTregs)一过性和大量增加。总体而言，使用CD34-DC疫苗是可行的、安全的和无毒的。可以检测到特异性的抗肿瘤免疫反应。然而，我们的数据强调，IL-2是体内nTregs的有效诱导者，因此可能对癌症免疫治疗产生负面影响。
Cytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34(+) cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining, patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific antitumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy.