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Oncotarget. 2016 Jun 21;7(25):37893-37905. doi: 10.18632/oncotarget.9247.

Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1.

Author information

1
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
2
Department of Translational Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
3
Flow Cytometry Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
4
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
5
Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
6
Department of Cutaneous Data Management, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

Abstract

Intralesional (IL) therapy is under investigation to treat dermal and subcutaneous metastatic cancer. Rose bengal (RB) is a staining agent that was originally used by ophthalmologists and in liver function studies. IL injection of RB has been shown to induce regression of injected and uninjected tumors in murine models and clinical trials. In this study, we have shown a mechanism of tumor-specific immune response induced by IL RB. In melanoma-bearing mice, IL RB induced regression of injected tumor and inhibited the growth of bystander lesions mediated by CD8+ T cells. IL RB resulted in necrosis of tumor cells and the release of High Mobility Group Box 1 (HMGB1), with increased dendritic cell (DC) infiltration into draining lymph nodes and the activation of tumor-specific T cells. Treatment of DC with tumor supernatants increased the ability of DCs to stimulate T cell proliferation, and blockade of HMGB1 in the supernatants suppressed DC activity. Additionally, increased HMGB1 levels were measured in the sera of melanoma patients treated with IL RB. These results support the role of IL RB to activate dendritic cells at the site of tumor necrosis for the induction of a systemic anti-tumor immune response.

KEYWORDS:

dendritic cells; high mobility group box 1; intralesional therapy; melanoma; rose bengal

PMID:
27177220
PMCID:
PMC5122358
DOI:
10.18632/oncotarget.9247
[Indexed for MEDLINE]
Free PMC Article

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