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Open AccessArticle

Selective Killing of Activated T Cells by 5-Aminolevulinic Acid Mediated Photodynamic Effect: Potential Improvement of Extracorporeal Photopheresis

1
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, N-0379 Oslo, Norway
2
Department of Clinical and Molecular Medicine, NTNU-Norwegian University of Science and Technology, N-7491 Trondheim, Norway
3
Department of Hematology, St. Olavs University Hospital HF, N-7491 Trondheim, Norway
4
Department of Dermatology, St. Olavs University Hospital HF, N-7491 Trondheim, Norway
5
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, N-0379 Oslo, Norway
6
Department of Cancer Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, N-0379 Oslo, Norway
7
Department of Optical Science and Engineering, The School of Information Science and Technology, Fudan University, Shanghai 200433, China
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(2), 377; https://doi.org/10.3390/cancers12020377
Received: 21 January 2020 / Revised: 28 January 2020 / Accepted: 4 February 2020 / Published: 6 February 2020
(This article belongs to the Special Issue Photodynamic Therapy (PDT) in Oncology)
Extracorporeal photopheresis (ECP), a modality that exposes isolated leukocytes to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light, is used to treat conditions such as cutaneous T-cell lymphoma and graft-versus-host disease. However, the current procedure of ECP has limited selectivity and efficiency; and produces only partial response in the majority of treated patients. Additionally, the treatment is expensive and time-consuming, so the improvement for this modality is needed. In this study, we used the concept of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor of an endogenously synthesized photosensitizer protoporphyrin IX (PpIX) in combination with blue light to explore the possibility of targeting activated human blood T cells ex vivo. With various T-cell activation protocols, a high ALA-induced PpIX production took place in activated CD3+, CD4+CD25+, and CD8+ T cell populations with their subsequent killing after blue light exposure. By contrast, resting T cells were much less damaged by the treatment. The selective and effective killing effect on the activated cells was also seen after co-cultivating activated and resting T cells. Under our clinically relevant experimental conditions, ALA-PDT killed activated T cells more selectively and efficiently than 8-MOP/UV-A. Monocyte-derived dendritic cells (DCs) were not affected by the treatment. Incubation of ALA-PDT damaged T cells with autologous DCs induced a downregulation of the co-stimulatory molecules CD80/CD86 and also upregulation of interleukin 10 (IL-10) and indoleamine 2,3-dioxygenase expression, two immunosuppressive factors that may account for the generation of tolerogenic DCs. Overall, the data support the potential use of ALA-PDT strategy for improving ECP by selective and effective killing of activated T cells and induction of immune tolerance. View Full-Text
Keywords: extracorporeal photopheresis; photodynamic therapy; cutaneous T cell lymphoma; graft-versus-host disease; 5-aminolevulinic acid; 8-methoxypsoralen; protoporphyrin IX; heme biosynthesis pathway; PBMC; T-cell activation extracorporeal photopheresis; photodynamic therapy; cutaneous T cell lymphoma; graft-versus-host disease; 5-aminolevulinic acid; 8-methoxypsoralen; protoporphyrin IX; heme biosynthesis pathway; PBMC; T-cell activation
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MDPI and ACS Style

Darvekar, S.; Juzenas, P.; Oksvold, M.; Kleinauskas, A.; Holien, T.; Christensen, E.; Stokke, T.; Sioud, M.; Peng, Q. Selective Killing of Activated T Cells by 5-Aminolevulinic Acid Mediated Photodynamic Effect: Potential Improvement of Extracorporeal Photopheresis. Cancers 2020, 12, 377.

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