Photodynamic Therapy-Based Dendritic Cell Vaccination Suited to Treat Peritoneal Mesothelioma

Our plain-English summary of Photodynamic Therapy-Based Dendritic Cell Vaccination Suited to Treat Peritoneal Mesothelioma, by N. Trempolec, B. Doix, C. Degavre, et al (Cancers, 2020).

The study

• Authors: N. Trempolec, B. Doix, C. Degavre, D. Brusa, C. Bouzin, O. Riant, O. Feron
• Journal: Cancers
• Published: 2020;12(3)
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The potential of dendritic cell (DC)-based immunotherapy to treat cancer is, nowadays, well documented. Still, the clinical success of immune checkpoint inhibitors has dampened the interest in anticancer DC vaccination. For highly life-threatening tumors that are regarded as nonimmunogenic, such as mesothelioma, however, T helper 1 immunity-biased DC-based immunotherapy could still represent an attractive strategy. In this study, we took advantage of photodynamic therapy (PDT) to induce immunogenic cell death to generate mesothelioma cell lysates for DC priming and evaluated such a vaccine to treat peritoneal mesothelioma. We found that the white light in vitro activation of the photosensitizer OR141 led to mesothelioma cell death, together with the release of bona fide danger signals that promote DC maturation. The administration of a PDT-based DC vaccine to mice bearing peritoneal mesothelioma led to highly significant survival when compared with sham or control animals treated with anti-CTLA4 antibodies. This was further supported by a strong CD8+ and CD4+ T cell response, characterized by an increased proliferation, cytotoxic activities and the expression of activation markers, including interferon gamma (IFN). Moreover, the PDT-based DC vaccine led to a significant increase in IFN+ T cells infiltered within mesothelioma, as determined by flow cytometry and immunohistochemistry. Finally, in vivo tracking of intraperitoneally administered DCs led us to document rapid chemotaxis towards tumor-occupied lymphatics (vs. lipopolysaccharide (LPS)-treated DC). DCs pulsed with PDT-killed mesothelioma cells also exhibited a significant increase in CCR7 receptors, together with an intrinsic capacity to migrate towards the lymph nodes. Altogether, these results indicate that PDT-based DC vaccination is particularly suited to induce a potent immune response against peritoneal mesothelioma.

In plain English

This was a laboratory study in cells and mice that tested an experimental vaccine against peritoneal mesothelioma. It did not study asbestos exposure. The authors killed mouse mesothelioma cells (lines Ab1 and Ab12) using photodynamic therapy, in which a drug called OR141 is activated by white light. They used the dead cells to prime dendritic cells, a type of immune cell, and injected these into the abdomen of BALB/c mice carrying Ab1 mesothelioma tumors. Light-activated OR141 killed mesothelioma cells from a dose of 1 µM and released danger signals that promote dendritic cell maturation. At day 55, 78% of vaccinated mice were alive, compared with 30% of mice given anti-CTLA4 antibodies and 7% of sham-treated mice. Vaccinated mice showed stronger CD8+ and CD4+ T cell responses and more CD8+ T cells inside their tumors. Their dendritic cells moved toward tumor areas within 15 minutes, while LPS-treated dendritic cells mainly stayed near the injection point. The authors concluded that this approach was particularly suited to induce a potent immune response against peritoneal mesothelioma. They noted that the abdominal injection route was likely to account for a large part of the effects.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiments: in vitro cell studies and animal (mouse) experiments
• Who was studied: Mouse mesothelioma cell lines Ab1 and Ab12, and BALB/c mice injected intraperitoneally with luciferase-expressing Ab1 mesothelioma cells (10 to 15 mice per group in the survival experiment), studied at UCLouvain, Belgium
• Exposure: No asbestos exposure was studied. The treatment tested was a dendritic cell vaccine primed with mesothelioma cells killed by white-light-activated OR141 (10 µM), given into the abdomen weekly for 3 weeks. It was compared with anti-CTLA4 antibodies, LPS-treated dendritic cells, and sham (PBS) treatment.
• Main results:
  • In cultured mesothelioma cells, light-activated OR141 caused cell death from a dose of 1 µM.
  • In mice with Ab1 mesothelioma, 78% of mice given the PDT-based dendritic cell vaccine were alive at day 55, compared with 30% of mice given anti-CTLA4 treatment and 7% of sham-treated mice.
  • Spleen cells from vaccinated mice showed significantly greater CD8+ T cell expansion on re-exposure to Ab1 mesothelioma cells than spleen cells from anti-CTLA4-treated mice.
  • After a single vaccine injection, tumors in the PDT-based vaccine group had significantly more CD8+ T cells than tumors in the control group and the LPS-treated dendritic cell vaccine group.
  • Dendritic cells primed with OR141-killed mesothelioma cells moved toward tumor areas within 15 minutes of injection, while LPS-treated dendritic cells mainly stayed near the injection point.
  • Six days after vaccination, the density of dendritic cells inside tumors did not differ significantly between the LPS-treated dendritic cell vaccine and the PDT-based vaccine.
• The authors' conclusion: The authors concluded that PDT-based dendritic cell vaccination is particularly suited to induce a potent immune response against peritoneal mesothelioma.
• Limitations the authors state:
  • The authors noted that the peritoneal (abdominal) route of administration was likely to account for a large part of the vaccine effects they reported.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Immunotherapy, checkpoint inhibitors, Mesothelioma, Immunohistochemistry.

Related studies

• WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome — Z.N. Berneman, M. De Laere, et al. (2025)
• Combined quetiapine and radiation therapy approach to treat mesothelioma-initiating cells and increase survival in a mouse model of mesothelioma — A. Cardenas, E. Arambula, et al. (2025)
• Anti-cancer therapy using dendritic cells and apoptotic tumour cells: pre-clinical data in human mesothelioma and acute myeloid leukaemia — M. Grégoire, C. Ligeza-Poisson, et al. (2003)
• Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials — D.W. Dumoulin, R. Cornelissen, et al. (2021)
• Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS — P.L. de Goeje, Y. Klaver, et al. (2018)
• Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma — M. van Gulijk, B. Belderbos, et al. (2023)

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