Oncotarget

Research Papers:

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

Hao Liu, Pasquale Patrick Innamarato, Krithika Kodumudi, Amy Weber, Satoshi Nemoto, John L. Robinson, Georgina Crago, Timothy McCardle, Erica Royster, Amod A. Sarnaik and Shari Pilon-Thomas _

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Oncotarget. 2016; 7:37893-37905. https://doi.org/10.18632/oncotarget.9247

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Abstract

Hao Liu1, Pasquale Patrick Innamarato1, Krithika Kodumudi1, Amy Weber1, Satoshi Nemoto3, John L. Robinson2, Georgina Crago4, Timothy McCardle5, Erica Royster6, Amod A. Sarnaik1,4,*, Shari Pilon-Thomas1,4,*

1Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

2Flow Cytometry Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

3Department of Translational Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

4Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

5Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

6Department of Cutaneous Data Management, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

*Shared senior authors

Correspondence to:

Shari Pilon-Thomas, e-mail: Shari.Pilon-Thomas@moffitt.org

Keywords: rose bengal, high mobility group box 1, dendritic cells, melanoma, intralesional therapy

Received: January 06, 2016    Accepted: April 26, 2016    Published: May 09, 2016

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.


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