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

María Julia Lamberti; Fátima María Mentucci; Viviana Alicia Rivarola; Mariana Maccioni; Natalia Belén Rumie Vittar

doi:10.1117/12.2525429

7 August 2019 Novel mechanism of dendritic cell maturation by dying/death tumor cells via photodynamic modulation of type 1 interferon pathway

María Julia Lamberti, Fátima María Mentucci, Viviana Alicia Rivarola, Mariana Maccioni, Natalia Belén Rumie Vittar

Author Affiliations +

Proceedings Volume 11070, 17th International Photodynamic Association World Congress; 110703L (2019) https://doi.org/10.1117/12.2525429
Event: 17th International Photodynamic Association World Congress, 2019, Cambridge, Massachusetts, United States

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.

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Citation Download Citation

María Julia Lamberti, Fátima María Mentucci, Viviana Alicia Rivarola, Mariana Maccioni, and Natalia Belén Rumie Vittar "Novel mechanism of dendritic cell maturation by dying/death tumor cells via photodynamic modulation of type 1 interferon pathway", Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110703L (7 August 2019); https://doi.org/10.1117/12.2525429

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