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Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1
- Source :
- Oncotarget
- Publication Year :
- 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.
- Subjects :
- 0301 basic medicine
Male
Necrosis
high mobility group box 1
T-Lymphocytes
Melanoma, Experimental
Pilot Projects
CD8-Positive T-Lymphocytes
rose bengal
Mice
0302 clinical medicine
HMGA1a Protein
Melanoma
Middle Aged
3. Good health
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
intralesional therapy
Tumor necrosis factor alpha
Female
medicine.symptom
Research Paper
Adult
T cell
Antineoplastic Agents
03 medical and health sciences
Young Adult
Immune system
Cell Line, Tumor
medicine
melanoma
Animals
Humans
dendritic cells
Aged
Cell Proliferation
business.industry
Dendritic cell
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
HEK293 Cells
Immunology
Cancer research
Leukocytes, Mononuclear
NIH 3T3 Cells
Liver function
business
CD8
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 25
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....37547c3b53efb432050089b425fe52fb