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Photodynamic Modulation of Type 1 Interferon Pathway on Melanoma Cells Promotes Dendritic Cell Activation
María Julia Lamberti1, Fátima María Mentucci1, Emiliano Roselli2
1Departamento de Biología Molecular, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Instituto de Biotecnología Ambiental y Salud, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
Frontiers in Immunology
|November 30, 2019
Summary
Photodynamic therapy (PDT) upregulates type-I-interferons (IFN-1) in melanoma cells, enhancing dendritic cell maturation. This finding highlights PDT
Area of Science:
- Immunology
- Oncology
- Photochemistry
Background:
- Type-I-interferons (IFN-1) play a crucial role in anti-cancer immune responses, including immune surveillance and tumor development control.
- IFN-1s are emerging as damage-associated molecular patterns (DAMPs) and are essential for inducing immunogenic cell death (ICD).
- Photodynamic therapy (PDT) is a cancer treatment involving photosensitizers and light activation, known to induce ICD via reactive oxygen species (ROS).
Purpose of the Study:
- To investigate the effect of photodynamic therapy (PDT) on type-I-interferon (IFN-1) expression in melanoma cells.
- To explore the impact of PDT-induced IFN-1 on dendritic cell (DC) maturation and function.
- To assess the potential of PDT in modulating the IFN-1 pathway for adoptive immunotherapy.
Main Methods:
- Administration of methyl-aminolevulinic acid (Me-ALA) to induce endogenous protoporphyrin IX (PpIX) photosensitizer in B16-OVA melanoma cells.
- Activation of PpIX with visible light to induce oxidative ER-stress mediated apoptotic cell death.
- Analysis of IFN-1 pathway activation, including IRF-3 phosphorylation, STAT1 activation, and ISG expression (CXCL10, MX1, ISG15).
- Assessment of dendritic cell (DC) maturation markers (CD80, MHC-II) and chemotaxis in response to PDT-treated melanoma cells.
Main Results:
- PDT treatment of melanoma cells resulted in significant upregulation of IFN-α/β transcripts in vitro.
- This IFN-1 upregulation was associated with IRF-3 phosphorylation, STAT1 activation, and increased expression of cGAS and downstream ISGs.
- PDT-treated melanoma cells induced IFN-1-dependent phenotypic maturation of monocyte-derived dendritic cells (DCs), enhancing co-stimulatory signals and tumor-directed chemotaxis.
Conclusions:
- PDT effectively induces oxidative ER-stress mediated apoptosis in melanoma cells.
- PDT treatment of melanoma cells represents a novel strategy for upregulating the IFN-1 pathway.
- PDT's ability to modulate the IFN-1 pathway and promote DC maturation highlights its potential as an immunotherapy adjuvant.
