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Open Access 01-06-2020 | Photodynamic Therapy | Original Article

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy

Authors: Malgorzata Wachowska, Joanna Stachura, Katarzyna Tonecka, Klaudyna Fidyt, Agata Braniewska, Zuzanna Sas, Iwona Kotula, Tomasz Piotr Rygiel, Louis Boon, Jakub Golab, Angelika Muchowicz

Published in: Cancer Immunology, Immunotherapy | Issue 6/2020

Abstract

It was previously reported that the activation of antitumor immune response by photodynamic therapy (PDT) is crucial for its therapeutic outcome. Excessive PDT-mediated inflammation is accompanied by immunosuppressive mechanisms that protect tissues from destruction. Thus, the final effect of PDT strongly depends on the balance between the activation of an adoptive arm of immune response and a range of activated immunosuppressive mechanisms. Here, with flow cytometry and functional tests, we evaluate the immunosuppressive activity of tumor-associated myeloid cells after PDT. We investigate the antitumor potential of PDT combined with indoleamine 2,3-dioxygenase 1 (IDO) inhibitor in the murine 4T1 and E0771 orthotopic breast cancer models. We found that the expression of IDO, elevated after PDT, affects the polarization of T regulatory cells and influences the innate immune response. Our results indicate that, depending on a therapeutic scheme, overcoming IDO-induced immunosuppressive mechanisms after PDT can be beneficial or can lead to a systemic toxic reaction. The inhibition of IDO, shortly after PDT, activates IL-6-dependent toxic reactions that can be diminished by the use of anti-IL-6 antibodies. Our results emphasize that deeper investigation of the physiological role of IDO, an attractive target for immunotherapies of cancer, is of great importance.

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Title: Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy
Authors: Malgorzata Wachowska
Joanna Stachura
Katarzyna Tonecka
Klaudyna Fidyt
Agata Braniewska
Zuzanna Sas
Iwona Kotula
Tomasz Piotr Rygiel
Louis Boon
Jakub Golab
Angelika Muchowicz
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keyword: Photodynamic Therapy
Published in: Cancer Immunology, Immunotherapy / Issue 6/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02528-5

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