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肿瘤细胞裂解物脉冲 CD8α+树突状细胞免疫疗法调节肿瘤内和脾脏淋巴细胞亚群。

Immunotherapy with tumor cell lysate-pulsed CD8α+ dendritic cells modulates intra-tumor and spleen lymphocyte subpopulations.

机构信息

Immunology Department, Qazvin University of Medical Sciences, Qazvin, Iran.

出版信息

Neoplasma. 2013;60(5):525-32. doi: 10.4149/neo_2013_068.

DOI:10.4149/neo_2013_068
PMID:23790171
Abstract

Using cellular adjuvants including dendritic cells (DCs) has provided a promising approach in immunotherapy of cancer. Our previous study showed that mice immunization with tumor cell lysate-pulsed DCs (TL-CD8α+DCs) could significantly suppress the tumor growth and increase mice survival. The aim of the present study was to investigate the impact of TL-CD8α+DC vaccine on intra-tumor and spleen lymphocyte subpopulations in tumor-bearing mice. ABalb/c mouse model of fibrosarcoma was used and changes in various lymphocyte subpopulations including CD4+, CD8+ and CD4+CD25+Foxp3+ T cells in mice immunized with TL-CD8α+ DCs were studied. The cytotoxic activity of the lymphocytes and tumor growth inhibitory rate were also measured. Immunotherapy with TL-CD8α+ DCs significantly enhanced both CD4+ and CD8+ lymphocytes, whereas decreased CD4+CD25+ Foxp3+ regulatory T cells as well as the tumor growth rate. There was also a decrease in the ratio of regulatory T cells to CD4+ and to CD8+ lymphocytes in both the tumor and spleen tissues as compared to that in the non-immunized control mice. Immunization with TL-CD8α+ DCs as well as CD8α+ DCs significantly increased the splenocytes cytotoxic activity by 45.1% and 18.2% of control, respectively. In conclusion, the current study indicated that TL-CD8α+ DCs can enhance tumor immunity against the fibrosarcoma by enhancing both the CD4+ and CD8+ lymphocytes and reducing regulatory T cells. This finding suggests the usefulness of TL-CD8α+DCs vaccine for cancer treatment.

摘要

使用细胞佐剂,包括树突状细胞(DC),为癌症的免疫治疗提供了一种很有前途的方法。我们之前的研究表明,用肿瘤细胞裂解物脉冲化的 DC(TL-CD8α+DC)免疫的小鼠可以显著抑制肿瘤生长并提高小鼠的存活率。本研究旨在探讨 TL-CD8α+DC 疫苗对荷瘤小鼠肿瘤内和脾脏淋巴细胞亚群的影响。使用 ABalb/c 小鼠纤维肉瘤模型,研究了 TL-CD8α+DC 免疫的小鼠中各种淋巴细胞亚群(包括 CD4+、CD8+和 CD4+CD25+Foxp3+T 细胞)的变化,并测量了淋巴细胞的细胞毒性活性和肿瘤生长抑制率。TL-CD8α+DC 免疫治疗显著增强了 CD4+和 CD8+淋巴细胞,而降低了 CD4+CD25+Foxp3+调节性 T 细胞以及肿瘤生长速度。与未免疫对照小鼠相比,肿瘤和脾脏组织中调节性 T 细胞与 CD4+和 CD8+淋巴细胞的比值也降低。TL-CD8α+DC 以及 CD8α+DC 免疫分别使脾细胞细胞毒性活性增加了 45.1%和 18.2%。总之,本研究表明,TL-CD8α+DC 可以通过增强 CD4+和 CD8+淋巴细胞并减少调节性 T 细胞来增强对纤维肉瘤的肿瘤免疫力。这一发现表明 TL-CD8α+DC 疫苗在癌症治疗中的有用性。

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