Systemic antitumor effect of intratumoral injection of dendritic cells in combination with local photodynamic therapy
Systemic antitumor effect of intratumoral injection of dendritic cells in combination with local photodynamic therapy
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DOI：
10.1158/1078-0432.ccr-05-1986
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发表时间：
2006-04-15
影响因子：
11.5
通讯作者：
Engleman, EG
中科院分区：
文献类型：
--
作者：
Saji, H;Song, WR;Engleman, EG
目的：光动力疗法（PDT），临床上用于癌症的姑息治疗，诱导局部肿瘤细胞死亡，但对未经治疗部位的肿瘤没有影响。本研究的目的是确定局部PDT随后瘤内注射幼稚树突状细胞（IT-DC）是否诱导全身性抗肿瘤免疫，所述抗肿瘤免疫可以抑制未处理的以及PDT + IT-DC处理的肿瘤的生长。分别用CT26结肠直肠癌细胞和1316黑色素瘤细胞，在肿瘤生长10至12天后，用单独的PDT或PDT后用IT-DC或IT-PBS处理肿瘤。在其他研究中，肿瘤同时建立在两个较低的侧腹或在一个侧腹和肺，但只有一个侧腹是treated. Results：而PDT也不是IT-DC单独是有效的，PDT + IT-DC根除了CT26和B16肿瘤在一个显着比例的动物和延长小鼠的生存期的肿瘤没有治愈。用PDT + IT-DC处理的小鼠的脾脏含有肿瘤特异性细胞毒性和IFN-γ分泌性T细胞，而对照组的脾脏没有。此外，从成功治疗的CT26无肿瘤小鼠中过继转移脾细胞可保护幼稚动物免受随后的CT26攻击，这主要由CD8 T细胞介导。最重要的是，PDT加IT-DC给药到一个肿瘤部位导致肿瘤消退在遥远的网站，包括多个lung metastases. Conclusions：PDT + IT-DC诱导小鼠有效的全身抗肿瘤免疫，并应在人类癌症的治疗中进行评估。
Purpose: Photodynamic therapy (PDT), which is used clinically for the palliative treatment of cancer, induces local tumor cell death but has no effect on tumors in untreated sites. The purpose of this study was to determine if local PDT followed by intratumoral injection of naive dendritic cells (IT-DC) induces systemic antitumor immunity that can inhibit the growth of untreated as well as PDT + IT-DC - treated tumors.Experimental Design: BALB/c or C57Bl/6 mice were injected s.c. with CT26 colorectal carcinoma cells and 1316 melanoma cells, respectively, and following 10 to 12 days of tumor growth, the tumors were treated with PDT alone or PDT followed by IT-DC or IT-PBS. In other studies, tumors were established simultaneously in both lower flanks or in one flank and in the lungs, but only one flank was treated.Results: Whereas neither PDT nor IT-DC alone was effective, PDT + IT-DC eradicated both CT26 and B16 tumors in a significant proportion of animals and prolonged the survival of mice of which the tumors were not cured. The spleens of mice treated with PDT + IT-DC contained tumor-specific cytotoxic and IFN-gamma-secreting T cells whereas the spleens of control groups did not. Moreover, adoptive transfer of splenocytes from successfully treated CT26 tumor-free mice protected naive animals from a subsequent challenge with CT26, and this was mediated mainly by CD8 T cells. Most importantly, PDT plus IT-DC administered to one tumor site led to tumor regression at distant sites, including multiple lung metastases.Conclusions: PDT + IT-DC induces potent systemic antitumor immunity in mice and should be evaluated in the treatment of human cancer.