H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):924-32. doi: 10.1016/j.ijrobp.2010.12.068. Epub 2011 Mar 11.
The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS).
Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10(7) DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed.
The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4(+) T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with (111)In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site.
Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.
本研究旨在确定树突状细胞（DC）瘤内给药联合分割外照射放疗（EBRT）对软组织肉瘤（STS）患者肿瘤特异性免疫应答的影响。
本研究纳入了 17 名患有大（>5cm）高级别 STS 的患者。他们在新辅助治疗中接受了 5040cGy 的 EBRT，分为 28 个剂量，每周 5 天给予，同时瘤内注射 10(7)个 DC，然后进行完全切除。DC 于治疗周期的第二个、第三个和第四个星期五注射。进行临床评估和免疫评估。
治疗耐受良好。在联合 EBRT/DC 治疗前，没有患者出现肿瘤特异性免疫应答；9 名患者（52.9%）出现了肿瘤特异性免疫应答，持续时间为 11 至 42 周。17 名患者中有 12 名（70.6%）在 1 年后无疾病进展。治疗导致肿瘤中 T 细胞大量积聚。肿瘤中 CD4(+)T 细胞的存在与联合治疗后出现的肿瘤特异性免疫应答呈正相关。髓源性抑制细胞的积累而不是调节性 T 细胞的积累与肿瘤特异性免疫应答的发展呈负相关。用（111）In 标记的 DC 进行的实验表明，这些抗原呈递细胞需要至少 48 小时才能开始从肿瘤部位迁移。
DC 瘤内给药联合 EBRT 是安全的，并诱导了抗肿瘤免疫应答。这表明该疗法具有前景，需要进一步在临床试验设计中进行测试，以评估临床疗效。
