Intratumoral dendritic cells and chemoradiation for the treatment of murine squamous cell carcinoma.
Intratumoral dendritic cells and chemoradiation for the treatment of murine squamous cell carcinoma.
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肿瘤内树突状细胞和化学放疗，用于治疗鼠鳞状细胞癌。
DOI：
10.1097/cji.0b013e3181880f1e
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Chang AE
中科院分区：
文献类型：
--
作者：
Moyer JS;Li J;Wei S;Teitz-Tennenbaum S;Chang AE
树突状细胞是一种有效的抗原呈递细胞，在体内和体外均具有显著的抗肿瘤作用。然而，树突状细胞作为一种免疫治疗方法的治疗效果受到肿瘤微环境中免疫耐受和主动免疫抑制的限制。为了解决这个问题，我们研究了在鳞状细胞癌小鼠模型中，同时进行全身化疗和局部分次放疗以增加瘤内树突状细胞注射的能力。瘤内单独注射树突状细胞对小鼠鳞状细胞癌侧腹肿瘤没有明显的抗肿瘤作用，但加用放化疗可使肿瘤明显消退。同时放化疗单独导致肿瘤生长减慢，但没有完全的肿瘤消退。放化疗和肿瘤内树突状细胞注射的结合使30%的小鼠存活率提高，肿瘤完全消退。肿瘤完全消退的小鼠在治疗后60天对相关肿瘤的重复攻击有部分抵抗。这些发现部分依赖于CD4+ T细胞、CD8+ T细胞和NK细胞的存在。放化疗可能通过增加瘤内细胞凋亡和减少瘤内调节性T细胞来增加瘤内树突状细胞注射。这项工作提示了肿瘤内树突状细胞治疗与更传统的放化疗策略的可能作用。
Dendritic cells are potent antigen presenting cells that have been shown to have significant antitumor effects in vitro and in vivo. However, the therapeutic efficacy of dendritic cells as an immunotherapeutic treatment has been limited by both immunologic tolerance and active immunosuppression in the tumor microenvironment. To address this problem, we examined the ability of concurrent systemic chemotherapy and local, fractionated radiation to augment intratumoral dendritic cell injections in a mouse model of squamous cell carcinoma. Intratumoral injections of dendritic cells alone did not have a significant antitumor effect in mice with squamous cell carcinoma flank tumors, but the addition of chemoradiation resulted in significant tumor regression. Concurrent chemoradiation alone resulted in slower tumor growth, but no complete tumor regressions. The combination of chemoradiation and intratumoral dendritic cell injections resulted in improved survival and complete tumor regression in 30% of mice. Mice with complete tumor regression were partially resistant to the repeat challenge with relevant tumor sixty days after treatment. These findings were partially dependent on the presence of CD4+ T cells, CD8+ T cells, and NK cells. Chemoradiation may augment intratumoral dendritic cell injections through increased intratumoral apoptosis as well as decreased intratumoral regulatory T cells. This work suggests a possible role for the use of intratumoral dendritic cell therapy with more traditional chemoradiation strategies.