Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids
Augmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. Non-Small Cell Lung Cancer (NSCLC) cell line...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/17/4119 |
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| author | Asta Valančiūtė Layla Mathieson Richard A. O’Connor Jamie I. Scott Marc Vendrell David A. Dorward Ahsan R. Akram Kevin Dhaliwal |
| author_facet | Asta Valančiūtė Layla Mathieson Richard A. O’Connor Jamie I. Scott Marc Vendrell David A. Dorward Ahsan R. Akram Kevin Dhaliwal |
| author_sort | Asta Valančiūtė |
| collection | DOAJ |
| description | Augmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. Non-Small Cell Lung Cancer (NSCLC) cell lines and primary human lung cancer organoids were evaluated in co-culture killing assays with MB-PDT and light emitting diodes (LEDs). ICD was characterised using immunoblotting, immunofluorescence, flow cytometry and confocal microscopy. Phototherapy with MB treatment and low energy LEDs decreased the proliferation of NSCLC cell lines inducing early necrosis associated with reduced expression of the anti-apoptotic protein, Bcl2 and increased expression of ICD markers, calreticulin (CRT), intercellular cell-adhesion molecule-1 (ICAM-1) and major histocompatibility complex I (MHC-I) in NSCLC cells. MB-PDT also potentiated CD8<sup>+</sup> T cell-mediated cytolysis of lung cancer via granzyme B in lung cancer cells and primary human lung cancer organoids. |
| first_indexed | 2024-03-10T01:59:37Z |
| format | Article |
| id | doaj.art-307052b9f7b347d494c65390a4a909d9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:59:37Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-307052b9f7b347d494c65390a4a909d92023-11-23T12:50:10ZengMDPI AGCancers2072-66942022-08-011417411910.3390/cancers14174119Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and OrganoidsAsta Valančiūtė0Layla Mathieson1Richard A. O’Connor2Jamie I. Scott3Marc Vendrell4David A. Dorward5Ahsan R. Akram6Kevin Dhaliwal7Translational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKTranslational Healthcare Technologies Group, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UKAugmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. Non-Small Cell Lung Cancer (NSCLC) cell lines and primary human lung cancer organoids were evaluated in co-culture killing assays with MB-PDT and light emitting diodes (LEDs). ICD was characterised using immunoblotting, immunofluorescence, flow cytometry and confocal microscopy. Phototherapy with MB treatment and low energy LEDs decreased the proliferation of NSCLC cell lines inducing early necrosis associated with reduced expression of the anti-apoptotic protein, Bcl2 and increased expression of ICD markers, calreticulin (CRT), intercellular cell-adhesion molecule-1 (ICAM-1) and major histocompatibility complex I (MHC-I) in NSCLC cells. MB-PDT also potentiated CD8<sup>+</sup> T cell-mediated cytolysis of lung cancer via granzyme B in lung cancer cells and primary human lung cancer organoids.https://www.mdpi.com/2072-6694/14/17/4119photodynamic therapylung cancerorganoidsimmunogenic cell death |
| spellingShingle | Asta Valančiūtė Layla Mathieson Richard A. O’Connor Jamie I. Scott Marc Vendrell David A. Dorward Ahsan R. Akram Kevin Dhaliwal Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids Cancers photodynamic therapy lung cancer organoids immunogenic cell death |
| title | Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids |
| title_full | Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids |
| title_fullStr | Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids |
| title_full_unstemmed | Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids |
| title_short | Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids |
| title_sort | phototherapeutic induction of immunogenic cell death and cd8 t cell granzyme b mediated cytolysis in human lung cancer cells and organoids |
| topic | photodynamic therapy lung cancer organoids immunogenic cell death |
| url | https://www.mdpi.com/2072-6694/14/17/4119 |
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