Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy
| Autor: | Katarzyna Tonecka, Joanna Stachura, Agata Braniewska, Angelika Muchowicz, Jakub Golab, Louis Boon, Tomasz P. Rygiel, Malgorzata Wachowska, Iwona Kotuła, Zuzanna Sas, Klaudyna Fidyt |
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| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
medicine.medical_treatment Immunology Photodynamic therapy Inflammation Systemic inflammation Flow cytometry 03 medical and health sciences Mice 0302 clinical medicine Immune system Immunology and Allergy Medicine Animals Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Indoleamine 2 3-dioxygenase 1 Interleukin 6 030304 developmental biology 0303 health sciences IL-6 Innate immune system biology medicine.diagnostic_test business.industry Interleukin-6 Cancer medicine.disease 3. Good health Oncology Photochemotherapy 030220 oncology & carcinogenesis biology.protein Cancer research Female Original Article medicine.symptom Epacadostat business |
| Zdroj: | Cancer Immunology, Immunotherapy |
| ISSN: | 1432-0851 |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1007/s00262-020-02528-5) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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