Establishment of Synergistic Chemoimmunotherapy for Head and Neck Cancer Using Peritumoral Immature Dendritic Cell Injections and Low-Dose Chemotherapies.
Establishment of Synergistic Chemoimmunotherapy for Head and Neck Cancer Using Peritumoral Immature Dendritic Cell Injections and Low-Dose Chemotherapies.
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DOI：
10.1016/j.tranon.2017.11.006
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发表时间：
2018-03
影响因子：
5
通讯作者：
Masuyama K
中科院分区：
文献类型：
--
作者：
Ishii H;Chikamatsu K;Igarashi S;Takahashi H;Sakamoto K;Higuchi H;Tanaka S;Matsuoka T;Masuyama K
缺乏具有强大免疫原性的肿瘤抗原，人类白细胞抗原的限制，以及通过调节性T细胞(Tregs)和髓系来源的抑制细胞进行免疫抑制，限制了晚期头颈癌(HNC)患者基于树突状细胞(DC)的免疫治疗。我们试图克服这些限制，并在宿主体内诱导有效的抗肿瘤免疫。通过体外实验观察小剂量多西紫杉醇(DTX)对DC成熟的影响，并设计瘤周直接注射未成熟DC(IDC)、OK-432和小剂量环磷酰胺(CTX)联合DTX的I期临床试验。低剂量DTX对IDC活性没有负面影响，反而促进了细胞成熟和IL-12的产生。有5名转移或复发的HNC患者参加了试验。所有患者均出现1~3级发热。有趣的是，在完成两个治疗周期的四名患者中，观察到CD8+效应T细胞增加，Tregs减少。所有患者都被判定为进展性疾病，但在五名患者中有两名在靶向转移灶的子集中观察到肿瘤消退。我们的结果表明，瘤周直接注射IDC联合OK-432和小剂量CTX+DTX是耐受性良好的，应该能改变晚期HNC患者T细胞亚群的免疫状况，改善免疫抑制。此外，我们关于小剂量DTX治疗对DC成熟的影响的体外数据可能有助于开发新的低剂量化疗和免疫治疗的联合疗法。
The lack of available tumor antigens with strong immunogenicity, human leukocyte antigen restriction, and immunosuppression via regulatory T-cells (Tregs) and myeloid-derived suppressor cells are limitations for dendritic cell (DC)–based immunotherapy in patients with advanced head and neck cancer (HNC). We sought to overcome these limitations and induce effective antitumor immunity in the host. The effect of low-dose docetaxel (DTX) treatment on DC maturation was examined in an ex vivo study, and a phase I clinical trial of combination therapy with direct peritumoral immature DC (iDC) injection with OK-432 and low-dose cyclophosphamide (CTX) plus DTX was designed. Low-dose DTX did not negatively affect iDC viability and instead promoted maturation and IL-12 production. Five patients with metastatic or recurrent HNC were enrolled for the trial. All patients experienced grade 1 to 3 fevers. Intriguingly, elevated CD8+ effector T-cells and reduced Tregs were observed in four patients who completed two treatment cycles. All patients were judged to have progressive disease, but tumor regressions were observed in a subset of targeted metastatic lesions in two of five patients. Our results show that the combination of direct peritumoral iDC injection with OK-432 and low-dose CTX plus DTX is well tolerated and should give rise to changing the immune profile of T-cell subsets and improvement of immunosuppression in advanced HNC patients. Additionally, our ex vivo data on the effect of low-dose DTX treatment on DC maturation may contribute to developing new combination therapies with low-dose chemotherapy and immunotherapy.
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影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
DOI：
10.1038/nrc3258
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Mellman, Ira;Coukos, George;Dranoff, Glenn
通讯作者：
Dranoff, Glenn
DOI：
10.1002/hed.24025
发表时间：
2016-04
期刊：
Head & neck
影响因子：
--
作者：
Whiteside TL;Ferris RL;Szczepanski M;Tublin M;Kiss J;Johnson R;Johnson JT
通讯作者：
Johnson JT
影响因子：
4.4
作者：
Tong, Charles C. L.;Kao, Johnny;Sikora, Andrew G.
通讯作者：
Sikora, Andrew G.