Repeated porphyrin lipoprotein-based photodynamic therapy controls distant disease in mouse mesothelioma via the abscopal effect

Our plain-English summary of Repeated porphyrin lipoprotein-based photodynamic therapy controls distant disease in mouse mesothelioma via the abscopal effect, by J. Lou, M. Aragaki, N. Bernards, et al (Nanophotonics, 2021).

The study

• Authors: J. Lou, M. Aragaki, N. Bernards, T. Kinoshita, J. Mo, Y. Motooka, T. Ishiwata, A. Gregor, T. Chee, Z. Chen, J. Chen, K. Kaga, S. Wakasa, G. Zheng, K. Yasufuku
• Journal: Nanophotonics
• Published: 2021;10(12):3279-3294
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

While photodynamic therapy (PDT) can induce acute inflammation in the irradiated tumor site, a sustained systemic, adaptive immune response is desirable, as it may control the growth of nonirradiated distant disease. Previously, we developed porphyrin lipoprotein (PLP), a ∼20 nm nanoparticle photosensitizer, and observed that it not only efficiently eradicated irradiated primary VX2 buccal carcinomas in rabbits, but also induced regression of nonirradiated metastases in a draining lymph node. We hypothesized that PLP-mediated PDT can induce an abscopal effect and we sought to investigate the immune mechanism underlying such a response in a highly aggressive, dual subcutaneous AE17-OVA+ mesothelioma model in C57BL/6 mice. Four cycles of PLP-mediated PDT was sufficient to delay the growth of a distal, nonirradiated tumor four-fold relative to controls. Serum cytokine analysis revealed high interleukin-6 levels, showing a 30-fold increase relative to phosphate-buffered solution (PBS) treated mice. Flow cytometry revealed an increase in CD4+ T cells and effector memory CD8+ T cells in non-irradiated tumors. Notably, PDT in combination with PD-1 antibody therapy prolonged survival compared to monotherapy and PBS. PLP-mediated PDT shows promise in generating a systemic immune response that can complement other treatments, improving prognoses for patients with metastatic cancers.

© 2021 Jenny Lou et al., published by De Gruyter, Berlin/Boston.

In plain English

This was a laboratory experiment in mice. It did not study asbestos exposure. The authors tested photodynamic therapy, in which an injected light-sensitive nanoparticle called porphyrin lipoprotein (PLP) is switched on by laser light. Female C57BL/6 mice had AE17-OVA+ mouse mesothelioma cells implanted under the skin of both hind legs, and only the left tumor was lit. Up to three treatment cycles did not slow growth of the unlit right tumor. With four cycles, the lit tumors were eradicated. Two weeks after the first injection, the unlit tumors were 4.2-fold and 4.1-fold smaller than in mice given laser alone or PLP alone. Treated mice had blood interleukin-6 levels 30.8-fold higher than mice given buffer solution (PBS). Their unlit tumors held a higher share of CD4+ T cells and a lower share of CD8+ T cells, but more of those CD8+ cells were effector memory cells. Adding an anti-PD-1 antibody gave the greatest delay in unlit tumor growth and a significant survival advantage over either treatment alone. The authors concluded that this therapy can induce this distant ('abscopal') effect in highly aggressive tumors.

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: Animal experiment (mouse tumor model, laboratory treatment study)
• Who was studied: Immunocompetent female C57BL/6 mice inoculated with 1 × 10^6 AE17-OVA+ mouse mesothelioma cells under the skin of both hind legs. Treatment groups mostly had 4 to 6 mice. Earlier tests used female athymic nude mice carrying human A549 and H2170 lung tumors. The work was done under the University Health Network, Toronto.
• Exposure: No asbestos exposure was studied. The 'exposure' was treatment: PLP (4 mg/kg) given intravenously, then 671 nm laser light (light dose chosen as 50 J/cm2) to the left tumor only, in one to four cycles (injections on days 0, 3, 7 and 10). In the combination experiment, an anti-PD-1 antibody (12.5 mg/kg) was injected into the abdominal cavity.
• Main results:
  • Light-dose test: no difference in survival between the 25, 50 and 75 J/cm2 groups (p greater than 0.05).
  • PDT given one to three times did not delay growth of the nonirradiated right tumors compared with laser control mice.
  • With four cycles, irradiated left tumors were eradicated. Two weeks after the first PLP injection, nonirradiated tumors in four-cycle PDT mice were 4.2-fold and 4.1-fold smaller than in laser and PLP controls, respectively.
  • After four PDT cycles, serum IL-6 was significantly raised: 30.8-, 66.8- and 52.1-fold over PBS, PLP and laser controls.
  • Serum IL-2 and IFN-γ did not differ between treatment groups.
  • In nonirradiated tumors of PDT mice, the percentage of CD4+ T cells was higher than in all control groups.
  • In nonirradiated tumors of PDT mice, CD8+ T cells were 5.4-fold and 7.0-fold lower than in PBS and PBS + laser mice, respectively. Effector memory CD8+ T cells were 2.2-fold and 2.7-fold higher than in PLP or PBS mice.
  • Mice given combined PDT and anti-PD-1 antibody had the greatest delay in nonirradiated tumor growth and a significant survival advantage over PDT alone or antibody alone.
  • Mice given either single treatment survived longer than PBS-treated mice.
• The authors' conclusion: The authors concluded that PLP-mediated PDT can induce the abscopal effect in highly aggressive tumors. They added that combining it with anti-PD-1 antibody improved survival of mice with AE17-OVA+ mesotheliomas compared with either treatment alone.
• Limitations the authors state:
  • The role of calreticulin in this mouse model needs more investigation.
  • Serum globulins were not separated into alpha, beta and gamma types.
  • The role of antibody-based (humoral) immunity in the effect was not determined.
  • The check of liver effects of repeated PDT was described as preliminary.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Inflammation, Carcinoma, Cytokine.

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