In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis
Background Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation...
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BMJ Publishing Group
2024-11-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/11/e009752.full |
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| author | Davide Brusa Caroline Bouzin Charline Degavre Anouk Lepez Sebastien Ibanez Clémence François Katarzyna Głowacka Céline Guilbaud Florine Laloux-Morris Hrag Esfahani Olivier Feron |
| author_facet | Davide Brusa Caroline Bouzin Charline Degavre Anouk Lepez Sebastien Ibanez Clémence François Katarzyna Głowacka Céline Guilbaud Florine Laloux-Morris Hrag Esfahani Olivier Feron |
| author_sort | Davide Brusa |
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| description | Background Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8+ T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes.Methods We used three-dimensional (3D) heterotypic spheroids made of cancer cells, exposed them to a white light-activated OR141 photosensitizer (PS), and subsequently complexified them by adding iDC and naive lymphocytes. We next used a model of mouse peritoneal carcinomatosis and administered PDT using laparoscopy to locally induce photoactivation using the endoscope light. The immune response following adoptive transfer of iDC was tracked both in vivo and ex vivo using isolated immune cells from in situ vaccinated mice.Results Cancer cells undergoing PDT-induced cell death significantly increased ICD markers and the infiltration of iDCs in spheroids, relying on ferroptosis. These actions induced the sequential activation of CD8+ and CD4+ T cells as revealed by a significant spheroid 3D structure deterioration and, remarkably, were not recapitulated by conventional ferroptosis inducer RSL3. Using LED light from an endoscope for in situ photoactivation of PS enabled us to apply the vaccination modality in mice with peritoneal tumors. Consecutive intraperitoneal injection of iDCs resulted in delayed tumor growth, increased survival rates, and prevented tumor relapse on rechallenge. CD8+ T cell response was supported by depletion experiments, nodal detection of early activated T cells, and ex vivo T cell-induced cytotoxicity toward spheroids.Conclusions The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition. |
| format | Article |
| id | doaj-art-2a25882a95494256802b11db717ed152 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-2a25882a95494256802b11db717ed1522025-08-20T02:32:38ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-11-01121110.1136/jitc-2024-009752In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosisDavide Brusa0Caroline Bouzin1Charline Degavre2Anouk Lepez3Sebastien Ibanez4Clémence François5Katarzyna Głowacka6Céline Guilbaud7Florine Laloux-Morris8Hrag Esfahani9Olivier Feron10CytoFlux-Flow Cytometry and Cell Sorting Platform, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Brussels, Belgium9 Institute of Experimental and Clinical Research (IREC), IREC Imaging Platform (2IP RRID:SCR_023378), UCLouvain, Université catholique de Louvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumIPHY Platform, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Brussels, BelgiumInstitut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology and Therapeutics (FATH), Cancer Translational Research laboratory, UCLouvain, Brussels, BelgiumBackground Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8+ T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes.Methods We used three-dimensional (3D) heterotypic spheroids made of cancer cells, exposed them to a white light-activated OR141 photosensitizer (PS), and subsequently complexified them by adding iDC and naive lymphocytes. We next used a model of mouse peritoneal carcinomatosis and administered PDT using laparoscopy to locally induce photoactivation using the endoscope light. The immune response following adoptive transfer of iDC was tracked both in vivo and ex vivo using isolated immune cells from in situ vaccinated mice.Results Cancer cells undergoing PDT-induced cell death significantly increased ICD markers and the infiltration of iDCs in spheroids, relying on ferroptosis. These actions induced the sequential activation of CD8+ and CD4+ T cells as revealed by a significant spheroid 3D structure deterioration and, remarkably, were not recapitulated by conventional ferroptosis inducer RSL3. Using LED light from an endoscope for in situ photoactivation of PS enabled us to apply the vaccination modality in mice with peritoneal tumors. Consecutive intraperitoneal injection of iDCs resulted in delayed tumor growth, increased survival rates, and prevented tumor relapse on rechallenge. CD8+ T cell response was supported by depletion experiments, nodal detection of early activated T cells, and ex vivo T cell-induced cytotoxicity toward spheroids.Conclusions The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition.https://jitc.bmj.com/content/12/11/e009752.full |
| spellingShingle | Davide Brusa Caroline Bouzin Charline Degavre Anouk Lepez Sebastien Ibanez Clémence François Katarzyna Głowacka Céline Guilbaud Florine Laloux-Morris Hrag Esfahani Olivier Feron In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis Journal for ImmunoTherapy of Cancer |
| title | In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis |
| title_full | In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis |
| title_fullStr | In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis |
| title_full_unstemmed | In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis |
| title_short | In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis |
| title_sort | in situ endoscopic photodynamic therapy combined with immature dc vaccination induces a robust t cell response against peritoneal carcinomatosis |
| url | https://jitc.bmj.com/content/12/11/e009752.full |
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