Saji Hisashi, Song Wenru, Furumoto Katsuyoshi, Kato Harubumi, Engleman Edgar G
Department of Pathology, Stanford University School of Medicine, Palo Alto, California, USA.
Clin Cancer Res. 2006 Apr 15;12(8):2568-74. doi: 10.1158/1078-0432.CCR-05-1986.
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 naïve dendritic cells (IT-DC) induces systemic antitumor immunity that can inhibit the growth of untreated as well as PDT + IT-DC-treated tumors.
BALB/c or C57Bl/6 mice were injected s.c. with CT26 colorectal carcinoma cells and B16 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.
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 naïve 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.
PDT + IT-DC induces potent systemic antitumor immunity in mice and should be evaluated in the treatment of human cancer.
光动力疗法（PDT）临床上用于癌症的姑息治疗，可诱导局部肿瘤细胞死亡，但对未治疗部位的肿瘤无效。本研究的目的是确定局部PDT后瘤内注射未致敏树突状细胞（IT-DC）是否能诱导全身抗肿瘤免疫，从而抑制未治疗肿瘤以及经PDT+IT-DC治疗肿瘤的生长。
分别给BALB/c或C57Bl/6小鼠皮下注射CT26结肠癌细胞和B16黑色素瘤细胞，肿瘤生长10至12天后，肿瘤单独接受PDT治疗，或先接受PDT治疗，随后接受IT-DC或IT-PBS注射。在其他研究中，双侧下腹部或一侧腹部及肺部同时接种肿瘤，但仅对一侧腹部的肿瘤进行治疗。
单独使用PDT或IT-DC均无效，而PDT+IT-DC可使相当一部分动物的CT26和B16肿瘤消退，并延长未治愈小鼠的生存期。接受PDT+IT-DC治疗的小鼠脾脏中含有肿瘤特异性细胞毒性T细胞和分泌IFN-γ的T细胞，而对照组小鼠脾脏中则没有。此外，将成功治疗的CT26无瘤小鼠的脾细胞过继转移，可保护未致敏动物免受后续CT26攻击，这主要由CD8 T细胞介导。最重要的是，对一个肿瘤部位给予PDT加IT-DC可导致远处部位的肿瘤消退，包括多个肺转移灶。
PDT+IT-DC可在小鼠中诱导强大的全身抗肿瘤免疫，应在人类癌症治疗中进行评估。
