Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
J Immunol Res. 2022 Mar 25;2022:7508928. doi: 10.1155/2022/7508928. eCollection 2022.
The main purpose of our study was to determine the effect of dendritic cell (DC) transduction with lentiviral vectors carrying sequences of and/or genes on the level of antitumor activity and . We examined the ability of DCs to migrate to the tumor-draining lymph nodes and infiltrate tumor tissue and to activate the local and systemic antitumor response. On the 15th day, DCs genetically modified for production of IL-12 and/or IL-18 were administered peritumorally to C57BL/6 female mice with established MC38 tumors. Lymphoid organs and tumor tissue were collected from mice on the 3rd, 5th, and 7th days after a single administration of DCs for further analysis. Administration of DCs transduced for production of IL-12 alone and in combination with IL-18 increased the inflow and activity of CD4 and CD8 T lymphocytes in the tumor microenvironment and tumor-draining lymph nodes. We also found that even a single administration of such modified DCs could trigger a systemic antitumor response as well as inhibit tumor growth. Application of the developed DC-based vaccines may exert a favorable impact on stimulation of an antitumor immune response, especially if these DC vaccines are administered repeatedly.
我们研究的主要目的是确定转导树突状细胞(DC)的慢病毒载体携带和/或基因序列对肿瘤活性和的影响。我们研究了 DC 向肿瘤引流淋巴结迁移、浸润肿瘤组织以及激活局部和全身抗肿瘤反应的能力。在第 15 天,将产生 IL-12 和/或 IL-18 的基因修饰的 DC 瘤周给药于已建立 MC38 肿瘤的 C57BL/6 雌性小鼠。在单次给予 DC 后第 3、5 和 7 天,从小鼠中收集淋巴器官和肿瘤组织进行进一步分析。单独转导产生 IL-12 的 DC 以及与 IL-18 联合转导的 DC 的给药增加了肿瘤微环境和肿瘤引流淋巴结中 CD4 和 CD8 T 淋巴细胞的流入和活性。我们还发现,即使单次给予这种修饰的 DC 也可以引发全身性抗肿瘤反应并抑制肿瘤生长。基于 DC 的疫苗的应用可能对刺激抗肿瘤免疫反应产生有利影响,特别是如果这些 DC 疫苗反复给予。