Chen Zhuang, Xia Dajing, Bi Xuguang, Saxena Anurag, Sidhu Narinder, El-Gayed Ali, Xiang Jim
Department of Oncology, Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan S7N 4H4, Canada.
J Gene Med. 2005 Apr;7(4):506-17. doi: 10.1002/jgm.692.
Tumor metastasis and relapse are major obstacles in combating human malignant diseases. Neither radiotherapy alone nor injection of dendritic cells (DCs) can successfully overcome this problem. Radiation induces tumor cell apoptosis and necrosis, resulting in the release of tumor antigen and danger signals, which are favorable for DC capturing antigens and maturation. Hence, the strategy of combined irradiation and DC vaccine may be a novel approach for treating human malignancies and early metastasis.
To develop an effective combined therapeutic approach, we established a novel concomitant local tumor and liver metastases model through subcutaneous (s.c.) and intravenous (i.v.) injection. We selected the optimal time for DC injection after irradiation and investigated the antitumor effect of combining irradiation with DC intratumoral injection and the related mechanism.
Combined treatment with radiotherapy and DC vaccine could induce a potent antitumor immune response, resulting in a significant decrease in the rate of local tumor relapse and the numbers of liver metastases. The related mechanisms for this strong antitumor immunity of this combined therapy might be associated with the production of apoptotic and necrotic tumor antigens and heat shock proteins after irradiation, phagocytosis, migration and maturation of DCs, and induction of more efficient tumor-specific cytotoxic T lymphocyte activity through a cross-presentation pathway.
Co-administration of local irradiation and intratumoral DC injection may be a promising strategy for treating radiosensitive tumors and eliminating metastasis in the clinic.
肿瘤转移和复发是对抗人类恶性疾病的主要障碍。单独的放射治疗或注射树突状细胞（DCs）都无法成功克服这一问题。辐射诱导肿瘤细胞凋亡和坏死，导致肿瘤抗原和危险信号的释放，这有利于DC捕获抗原并成熟。因此，联合放疗和DC疫苗的策略可能是治疗人类恶性肿瘤和早期转移的一种新方法。
为了开发一种有效的联合治疗方法，我们通过皮下（s.c.）和静脉（i.v.）注射建立了一种新型的局部肿瘤与肝转移伴随模型。我们选择了放疗后DC注射的最佳时间，并研究了放疗与DC瘤内注射联合的抗肿瘤效果及相关机制。
放疗与DC疫苗联合治疗可诱导强大的抗肿瘤免疫反应，导致局部肿瘤复发率和肝转移灶数量显著降低。这种联合治疗强大抗肿瘤免疫的相关机制可能与放疗后凋亡和坏死肿瘤抗原及热休克蛋白的产生、DC的吞噬、迁移和成熟，以及通过交叉呈递途径诱导更有效的肿瘤特异性细胞毒性T淋巴细胞活性有关。
局部放疗与瘤内注射DC联合应用可能是临床治疗放射敏感性肿瘤和消除转移的一种有前景的策略。
