title: Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1.
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.
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Pasquale Patrick
authors.initials: PP
authors.lastname: Innamarato
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Krithika
authors.initials: K
authors.lastname: Kodumudi
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Weber
authors.affiliation: Department of Translational Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nemoto
authors.affiliation: Flow Cytometry Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Robinson
authors.affiliation: Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Georgina
authors.initials: G
authors.lastname: Crago
authors.affiliation: Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: McCardle
authors.affiliation: Department of Cutaneous Data Management, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Royster
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Amod A
authors.initials: AA
authors.lastname: Sarnaik
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.|Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Shari
authors.initials: S
authors.lastname: Pilon-Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D025741:HMGA1a Protein / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009336:Necrosis; D010865:Pilot Projects; D012395:Rose Bengal / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D025741:HMGA1a Protein; D012395:Rose Bengal
keywords: dendritic cells; high mobility group box 1; intralesional therapy; melanoma; rose bengal