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Proceedings Paper

Novel mechanism of dendritic cell maturation by dying/death tumor cells via photodynamic modulation of type 1 interferon pathway
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Paper Abstract

During the past decades, a growing body of evidence clearly indicates that type I IFNs (IFN-1) play a pivotal role in naturally occurring and therapy induced immune responses to cancer. In this context, we describe here a novel effect of photodynamic therapy (PDT): besides its potential to induce apoptosis, PDT elicited an autocrine/paracrine activation of IFN-1 pathway. In the current work, B16-OVA cells were sensitized with Me-ALA-induced protoporphyrin IX (PpIX) which preferentially localized in the endoplasmic reticulum prior to irradiation. Subsequent photoactivation of PpIX with red-light irradiation ignificantly stimulated tumor cells to induce autocrine IFN-1 transcription, concurrently with IRF-3 phosphorylation, at levels that were capable of activating STAT1 and enhancing ligand receptor (cGAS) and ISGs (CXCL10, MX1, ISG15) expression. Among the cellular and molecular pathways identified so far, type I IFNs are critical components for the host immune response against tumor, more specifically for the dendritic cell (DC) compartment. In this sense, PDT-treated melanoma cells induced paracrine IFN-1-dependent phenotypic maturation of monocyte-derived dendritic cells (DCs) by enhancing co-stimulatory signals (CD80, MHC-II) and tumor-directed chemotaxis (transwell migration assay). Collectively, our findings strongly demonstrate the effects of a novel danger signal released by cancer cells undergoing PDT on the maturation and activation of DCs, highlighting the potential added value of PDT in adoptive immunotherapy protocols.

Paper Details

Date Published: 7 August 2019
PDF: 9 pages
Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110703L (7 August 2019); doi: 10.1117/12.2525429
Show Author Affiliations
María Julia Lamberti, Univ. Nacional de Río Cuarto (Argentina)
Fátima María Mentucci, Univ. Nacional de Río Cuarto (Argentina)
Viviana Alicia Rivarola, Univ. Nacional de Río Cuarto (Argentina)
Mariana Maccioni, CIBICI-UNC (Argentina)
Natalia Belén Rumie Vittar, Univ. Nacional de Río Cuarto (Argentina)

Published in SPIE Proceedings Vol. 11070:
17th International Photodynamic Association World Congress
Tayyaba Hasan, Editor(s)

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