Document Type

Article

Publication Date

12-2018

Publication Title

Cancers

Volume

10

Issue

12

Pages

498 (19 pages)

DOI

10.3390/cancers10120498

Abstract

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell composition after intratumoral injection of pIL-12 GET. The number of immune memory cells was markedly increased in pIL-12 GET melanoma groups compared to control group. This was validated using flow cytometry to analyze peripheral blood mononuclear cells as well as delineating immune cell content using immunohistochemistry. Significant differences in multiple cell types were observed, including CD8+ T cells, regulatory T cells and myeloid cells, which were induced to mount a CD8+PD1 T cells immune response. Taken together, these findings suggest a basic understanding of the sequence of immune activity following pIL-12 GET and also illuminates that adjuvant immunotherapy can have a positive influence on the host immune response to cancer.

Comments

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

Original Publication Citation

Shi, G., Edelblute, C., Arpag, S., Lundberg, C., & Heller, R. (2018). IL-12 gene electrotransfer triggers a change in immune response within mouse tumors. Cancers (Basel), 10(12), 498. doi:10.3390/cancers10120498

ORCID

0000-0002-6188-4116 (Shi), 0000-0002-6449-4164 (Arpag), 0000-0003-1899-3859 (Heller)

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