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Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming
Photodynamic therapy (PDT) with redaporfin stimulates colon carcinoma (CT26), breast (4T1) and melanoma (B16F10) cells to display high levels of CD80 molecules on their surfaces. CD80 overexpression amplifies immunogenicity because it increases same cell (cis) CD80:PD-L1 interactions, which (i) disr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356828/ https://www.ncbi.nlm.nih.gov/pubmed/37468749 http://dx.doi.org/10.1038/s41598-023-38862-8 |
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author | Lobo, Catarina S. Mendes, Maria Inês P. Pereira, Diogo A. Gomes-da-Silva, Lígia C. Arnaut, Luis G. |
author_facet | Lobo, Catarina S. Mendes, Maria Inês P. Pereira, Diogo A. Gomes-da-Silva, Lígia C. Arnaut, Luis G. |
author_sort | Lobo, Catarina S. |
collection | PubMed |
description | Photodynamic therapy (PDT) with redaporfin stimulates colon carcinoma (CT26), breast (4T1) and melanoma (B16F10) cells to display high levels of CD80 molecules on their surfaces. CD80 overexpression amplifies immunogenicity because it increases same cell (cis) CD80:PD-L1 interactions, which (i) disrupt binding of T-cells PD-1 inhibitory receptors with their ligands (PD-L1) in tumour cells, and (ii) inhibit CTLA-4 inhibitory receptors binding to CD80 in tumour cells. In some cancer cells, redaporfin-PDT also increases CTLA-4 and PD-L1 expressions and virtuous combinations between PDT and immune-checkpoint blockers (ICB) depend on CD80/PD-L1 or CD80/CTLA-4 tumour overexpression ratios post-PDT. This was confirmed using anti-CTLA-4 + PDT combinations to increase survival of mice bearing CT26 tumours, and to regress lung metastases observed with bioluminescence in mice with orthotopic 4T1 tumours. However, the primary 4T1 responded poorly to treatments. Photoacoustic imaging revealed low infiltration of redaporfin in the tumour. Priming the primary tumour with high-intensity (~ 60 bar) photoacoustic waves generated with nanosecond-pulsed lasers and light-to-pressure transducers improved the response of 4T1 tumours to PDT. Penetration-resistant tumours require a combination of approaches to respond to treatments: tumour priming to facilitate drug infiltration, PDT for a strong local effect and a change in immunogenicity, and immunotherapy for a systemic effect. |
format | Online Article Text |
id | pubmed-10356828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103568282023-07-21 Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming Lobo, Catarina S. Mendes, Maria Inês P. Pereira, Diogo A. Gomes-da-Silva, Lígia C. Arnaut, Luis G. Sci Rep Article Photodynamic therapy (PDT) with redaporfin stimulates colon carcinoma (CT26), breast (4T1) and melanoma (B16F10) cells to display high levels of CD80 molecules on their surfaces. CD80 overexpression amplifies immunogenicity because it increases same cell (cis) CD80:PD-L1 interactions, which (i) disrupt binding of T-cells PD-1 inhibitory receptors with their ligands (PD-L1) in tumour cells, and (ii) inhibit CTLA-4 inhibitory receptors binding to CD80 in tumour cells. In some cancer cells, redaporfin-PDT also increases CTLA-4 and PD-L1 expressions and virtuous combinations between PDT and immune-checkpoint blockers (ICB) depend on CD80/PD-L1 or CD80/CTLA-4 tumour overexpression ratios post-PDT. This was confirmed using anti-CTLA-4 + PDT combinations to increase survival of mice bearing CT26 tumours, and to regress lung metastases observed with bioluminescence in mice with orthotopic 4T1 tumours. However, the primary 4T1 responded poorly to treatments. Photoacoustic imaging revealed low infiltration of redaporfin in the tumour. Priming the primary tumour with high-intensity (~ 60 bar) photoacoustic waves generated with nanosecond-pulsed lasers and light-to-pressure transducers improved the response of 4T1 tumours to PDT. Penetration-resistant tumours require a combination of approaches to respond to treatments: tumour priming to facilitate drug infiltration, PDT for a strong local effect and a change in immunogenicity, and immunotherapy for a systemic effect. Nature Publishing Group UK 2023-07-19 /pmc/articles/PMC10356828/ /pubmed/37468749 http://dx.doi.org/10.1038/s41598-023-38862-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lobo, Catarina S. Mendes, Maria Inês P. Pereira, Diogo A. Gomes-da-Silva, Lígia C. Arnaut, Luis G. Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
title | Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
title_full | Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
title_fullStr | Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
title_full_unstemmed | Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
title_short | Photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
title_sort | photodynamic therapy changes tumour immunogenicity and promotes immune-checkpoint blockade response, particularly when combined with micromechanical priming |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356828/ https://www.ncbi.nlm.nih.gov/pubmed/37468749 http://dx.doi.org/10.1038/s41598-023-38862-8 |
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