Intratumoral injection of dendritic cells overexpressing interleukin‑12 inhibits melanoma growth

Yao,Weirong; Li,Yingliang; Zeng,Lin; Zhang,Xiquan; Zhou,Zhiyong; Zheng,Meixue; Wan,Huiping

doi:10.3892/or.2019.7165

Intratumoral injection of dendritic cells overexpressing interleukin‑12 inhibits melanoma growth

Authors:
- Weirong Yao
- Yingliang Li
- Lin Zeng
- Xiquan Zhang
- Zhiyong Zhou
- Meixue Zheng
- Huiping Wan
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Affiliations: Oncology Department, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Graduate School, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: May 21, 2019 https://doi.org/10.3892/or.2019.7165
Pages: 370-376

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Abstract

The present study aimed to investigate the antitumor effects of an intratumoral injection of dendritic cells (DCs) overexpressing interleukin-12 (IL‑12) on melanoma. DCs, isolated from mouse spleen, were gene‑modified using an IL‑12 overexpression vector. Melanoma B6 cells were injected into C57BL/6 mice to generate tumors. Thereafter, DCs overexpressing IL‑12 were injected into the tumors, and tumor volume was subsequently measured. Pathological changes in tumor tissue were detected by hematoxylin and eosin staining. The expression of interleukin-4 (IL‑4) and IL‑12 in tumors was measured by enzyme‑linked immunosorbent assay, real‑time PCR and western blotting. DCs were successfully isolated and a lentivirus vector expressing IL‑12 was constructed. After intratumoral injection of phosphate‑buffered saline (control group), tumor cells exhibited malignant growth; whereas tumors injected with DCs (DC group) or DCs + empty vector (DC + vector group) exhibited a small amount of inflammatory cell infiltration and limited areas of tissue necrosis. In contrast, tumors injected with DCs overexpressing IL‑12 (DC + IL‑12 group) displayed severe tissue necrosis, loss of cell structure, and inflammatory cell infiltration. Compared with the control group, the tumor volumes were significantly lower in the DC, the DC + vector and the DC + IL‑12 groups, while the expression of IL‑12 and IL‑4 in the tumors was significantly higher. Importantly, the most marked changes in tumor volume and IL‑12 and IL‑4 expression were in the DC + IL‑12 group, which were significantly greater than those in tumors treated with unmodified DCs. Hence, intratumoral injection of DCs overexpressing IL‑12 exerted strong antitumor effects in melanoma, and biotherapy with DCs overexpressing IL‑12 is a potential treatment strategy for melanoma.

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