Selective Killing of Activated T Cells by 5-Aminolevulinic Acid Mediated Photodynamic Effect: Potential Improvement of Extracorporeal Photopheresis
Open accessAbstract
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.
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In antigen-presenting cells such as dendritic cells and macrophages, PpIX accumulation can occur regardless of cell activation.
“However, in antigen-presenting cells such as dendritic cells and macrophages, PpIX accumulation can occur regardless of cell activation [161,162].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [162]
The Results (§2.1 and §2.5; page unavailable) compare PpIX production in resting and activated T cells. Searches for dendritic cells, macrophages, and activation-independent PpIX accumulation found no passage addressing the claim about antigen-presenting cells. (LLM, conf=0.75)
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Cites
Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., Moan, J., & Peng, Q. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.12.889 · Cited by 4,716 · see citing works
Self-citationGomer, C. J. (1988) · Cited by 4,169 · see citing works
Stummer, W., Pichlmeier, U., Meinel, T., Wiestler, O. D., Zanella, F., & Reulen, H.-J. (2006) · The Lancet Oncology · doi:10.1016/s1470-2045(06)70665-9 · Cited by 3,423 · see citing works
Steinman, R. M., Hawiger, D., & Nussenzweig, M. C. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141040 · Cited by 3,124 · see citing works
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341 · see citing works
Treatment of Cutaneous T-Cell Lymphoma by Extracorporeal Photochemotherapy
Edelson, R. L., Berger, C. L., Gasparro, F. P., Jegasothy, B. V., HEALD, P. W., Wintroub, B. U., Vonderheid, E. C., Knobler, R., Wolff, K. S., Plewig, G., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198702053160603 · Cited by 1,197 · see citing works
Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase
Munn, D. H., Sharma, M. D., Lee, J. R., Jhaver, K. G., Johnson, T. S., Keskin, D. B., Marshall, B., Chandler, P., Antonia, S. J., Burgess, R. E., et al. (2002) · Science · doi:10.1126/science.1073514 · Cited by 1,028 · see citing works
Tryptophan and the immune response
Moffett, J., & Namboodiri, M. (2003) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.2003.t01-1-01177.x · Cited by 765 · see citing works
5-Aminolevulinic Acid-Based Photodynamic Therapy: Principles and Experimental Research
Peng, Q., Berg, K., Moan, J., Kongshaug, M., & Nesland, J. M. (1997) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1997.tb08549.x · Cited by 615 · see citing works
Self-citationStern, R. S., Thibodeau, L. A., Kleinerman, R. A., Parrish, J. A., Fitzpatrick, T. B., & 22 Participating Investigators (1979) · New England Journal of Medicine · doi:10.1056/nejm197904123001501 · Cited by 556 · see citing works
Hypericin in cancer treatment: more light on the way
Agostinis, P., Vantieghem, A., Merlevede, W. J., & de Witte, P. A. M. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00126-1 · Cited by 469 · see citing works
A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation
Braun, D., Longman, R., & Albert, M. L. (2005) · Blood · doi:10.1182/blood-2005-03-0979 · Cited by 390 · see citing works
T cell stimulation and expansion using anti-CD3/CD28 beads
Trickett, A. E., & Kwan, Y. L. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(03)00010-3 · Cited by 381 · see citing works
Morton, C. A., Szeimies, R. ‐., Sidoroff, A., & Braathen, L. R. (2013) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.12031 · Cited by 344 · see citing works
Stern, R. S., & Lange, R. (1988) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12464137 · Cited by 333 · see citing works
Archier, E., Devaux, S., Castela, E., Gallini, A., Aubin, F., Maître, M. L., Aractingi, S., Bachelez, H., Cribier, B. J., Joly, P., et al. (2012) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2012.04520.x · Cited by 311 · see citing works
Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins
Malik, Z., & Lugaci, H. (1987) · British Journal of Cancer · doi:10.1038/bjc.1987.246 · Cited by 292 · see citing works
Development and function of CD25+CD4+ regulatory T cells
Fehervari, Z. T., & Sakaguchi, S. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.01.004 · Cited by 216 · see citing works
Regulatory pathways in photodynamic therapy induced apoptosis
Agostinis, P., Breyssens, H., Buytaert, E., & Hendrickx, N. (2004) · Photochemical & Photobiological Sciences · doi:10.1039/b315237e · Cited by 196 · see citing works
Biagi, E., Biaso, I. D., Leoni, V., Gaipa, G., Rossi, V., Bugarin, C., Renoldi, G., Parma, M., Balduzzi, A., Perseghin, P., et al. (2007) · Transplantation · doi:10.1097/01.tp.0000267785.52567.9c · Cited by 155 · see citing works
Alfred, A., Taylor, P. C., Dignan, F. L., El‐Ghariani, K., Griffin, J., Gennery, A. R., Bonney, D. K., Das-Gupta, E. P., Lawson, S., Malladi, R. K., et al. (2017) · British Journal of Haematology · doi:10.1111/bjh.14537 · Cited by 141 · see citing works
Rittenhouse‐Diakun, K., Leengoed, H. V., Morgan, J., Hryhorenko, E., Paszkiewicz, G., Whitaker, J. E., & Oseroff, A. R. (1995) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1995.tb02356.x · Cited by 124 · see citing works
Furre, I. E., Shahzidi, S., Lukšiené, Ž., Møller, M. T. N., Borgen, E., Morgan, J., Tkacz-Stachowska, K., Nesland, J. M., & Peng, Q. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0510 · Cited by 84 · see citing works
Self-citationSide-effects of psoralen photochemotherapy (PUVA)
Wolff, K. (1990) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1990.tb02889.x · Cited by 83 · see citing works
Apoptosis, tolerance, and regulatory T cells – old wine, new wineskins
Ferguson, T. A., Stuart, P. M., Herndon, J., & Griffith, T. S. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00042.x · Cited by 72 · see citing works
Extracorporeal photopheresis: How, when, and why
Ward, D. M. (2011) · Journal of Clinical Apheresis · doi:10.1002/jca.20300 · Cited by 56 · see citing works
Furset, G., Fløisand, Y., & Sioud, M. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02695.x · Cited by 49 · see citing works
Self-citationPhotopheresis (extracorporeal photochemotherapy)
Trautinger, F., Just, U., & Knobler, R. (2012) · Photochemical & Photobiological Sciences · doi:10.1039/c2pp25144b · Cited by 36 · see citing works
Goussetis, E., Varela, I., & Tsirigotis, P. D. (2011) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2011.10.017 · Cited by 36 · see citing works
Morelli, A. E., & Larregina, A. T. (2016) · Stem Cells · doi:10.1002/stem.2326 · Cited by 35 · see citing works
Hryhorenko, E. A., Rittenhouse-Diakun, K., Harvey, N. S., Morgan, J., Stewart, C. C., & Oseroff, A. R. (1998) · PubMed · Cited by 35 · see citing works
Futterleib, J. S., Feng, H., Tigelaar, R. E., Choi, J., & Edelson, R. L. (2013) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2013.10.003 · Cited by 31 · see citing works
Hryhorenko, E. A., Rittenhouse-Diakun, K., Harvey, N. S., Morgan, J., Stewart, C. C., & Oseroff, A. R. (1998) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1998.tb09456.x · Cited by 31 · see citing works
Holien, T., Gederaas, O. A., Darvekar, S. R., Christensen, E., & Peng, Q. (2018) · Lasers in Surgery and Medicine · doi:10.1002/lsm.22806 · Cited by 19 · see citing works
Self-citationČunderlı́ková, B., Vasovič, V., Randeberg, L. L., Christensen, E., Warloe, T., Nesland, J. M., & Peng, Q. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.05.020 · Cited by 14 · see citing works
Self-citation- Self-citation
Flagged first, then by citations
1 of the 37 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Photodynamic viral inactivation: Recent advances and potential applications
Willis, J. A., Cheburkanov, V. D., Kassab, G., Soares, J. M., Blanco, K. C., Bagnato, V. S., & Yakovlev, V. V. (2021) · Applied Physics Reviews · doi:10.1063/5.0044713 · Cited by 58 · see citing works
Application of photodynamic therapy in immune-related diseases
Yang, D., Lei, S., Pan, K., Chen, T., Lin, J., Ni, G., Liu, J., Zeng, X. Y., Chen, Q., & Dan, H. (2021) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2021.102318 · Cited by 43 · see citing works
Photodynamic Therapy (PDT) in Oncology
Juarranz, Á., Gilaberte, Y., & González, S. (2020) · Cancers · doi:10.3390/cancers12113341 · Cited by 42 · see citing works
5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy
Howley, R., Chandratre, S., & Chen, B. (2023) · Bioengineering · doi:10.3390/bioengineering10040496 · Cited by 33 · see citing works
Recent advances in microneedles for tumor therapy and diagnosis
Lin, S., Cao, Y., Chen, J., Tian, Z., & Zhu, Y. (2021) · Applied Materials Today · doi:10.1016/j.apmt.2021.101036 · Cited by 32 · see citing works
Marcus, S. L., & de Souza, M. P. (2024) · Cancers · doi:10.3390/cancers16040740 · Cited by 29 · see citing works
Christensen, E., Foss, O. A., Quist-Paulsen, P., Staur, I., Pettersen, F., Holien, T., Juzenas, P., & Peng, Q. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13101558 · Cited by 10 · see citing works
Self-citationEspeland, K., Kleinauskas, A., Juzenas, P., Brech, A., Darvekar, S. R., Vasovič, V., Warloe, T., Christensen, E., Jahnsen, J., & Peng, Q. (2022) · Biomedicines · doi:10.3390/biomedicines10020232 · Cited by 7 · see citing works
Self-citationExtracorporeal Photopheresis: Does It Have a Potential Place Among Cell-based Therapies?
Parsonidis, P., & Wekerle, T. (2025) · Transplantation Direct · doi:10.1097/txd.0000000000001808 · Cited by 5 · see citing works
Christensen, E., Foss, O. A., Holien, T., Juzenas, P., & Peng, Q. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16060815 · Cited by 4 · see citing works
Self-citationEspeland, K., Christensen, E., Aandahl, A., Ulvær, A., Warloe, T., Kleinauskas, A., Darvekar, S. R., Juzenas, P., Vasovič, V., Peng, Q., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13206198 · Cited by 1 · see citing works
Self-citationBeyond 8-methoxypsoralen as the photosensitizer for extracorporeal photopheresis
Castillo‐Aleman, Y. M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.996973 · Cited by 1 · see citing works
Evaluation of the Cellular Resistance Process in Treated Cells Via Extracorporeal Photopheresis
Arjmand, B., Rezaei–Tavirani, M., Sherafat, S. J., Rezaei, M. S., Farahani, M., & Tavirani, M. R. (2023) · Journal of lasers in medical sciences · doi:10.34172/jlms.2023.46
Letter to the Editor. ALA in the treatment of glioblastoma
Hossain-Ibrahim, M. K. (2024) · Journal of neurosurgery · doi:10.3171/2023.11.jns232472
Current photodynamic therapy and emerging synergies in oncology
Thangeswaran, D., Chin, D. S., Balakrishnan, V., Sasidharan, S., Lai, H. W., & Tye, G. J. (2025) · Asia-Pacific Journal of Molecular Biology and Biotechnology · doi:10.35118/apjmbb.2025.033.2.03
ALA-PDT in the Treatment of Diseases of Hair Follicles and Sebaceous Glands
Liu, X., Zhang, L., Cao, Y., Cao, Z. W., Yang, J., Wang, B., & Wang, X. (2025) · Springer eBooks · doi:10.1007/978-981-96-8915-6_9
- Authors
- Darvekar, S., Juzenas, P., Oksvold, M., Kleinauskas, A., Holien, T., Christensen, E., Stokke, T., Sioud, M., & Peng, Q.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Sioud, Mouldy
- Peng, Qian
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2020-02-06
- Volume
- 12
- Issue
- 2
- Pages
- 377
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC7072277
- OpenAlex
- W3004705260
- Cited by
- 16
- References
- 37
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Helse Sør-Øst RHF (2016092, 2015075)
- reftforeningen (33608)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Dermatology › Cutaneous lymphoproliferative disorders research
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- 5-aminolevulinic acid, photodynamic therapy, extracorporeal photopheresis, activated T cells, protoporphyrin IX, blue light, 8-methoxypsoralen, T cell activation, dendritic cells, immune tolerance, IL-10, indoleamine 2,3-dioxygenase, CD80/CD86, cutaneous T-cell lymphoma, graft-versus-host disease
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