Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 17;193(2):276-286.
doi: 10.1093/bjd/ljaf102.

Evidence of immunogenic cell death (ICD) and ICD-dependent dendritic cell activation induced by extracorporeal photopheresis in patients with leukaemic forms of cutaneous T-cell lymphoma

Angelika Lackner  1 , Teresa Burner  1 , Marlene Huber  1 , Saptaswa Dey  2 , Stefan Aigner  1 , Veronika Buxhofer-Ausch  3   4 , Marija Geroldinger-Simic  4   5 , Christoph Iselin  6 , Yun-Tsan Chang  6 , Yi-Chien Tsai  6 , Sabine Altrichter  1   7 , Peter Wolf  2 , Susanne Kimeswenger  1 , Emmanuella Guenova  6   8 , Wolfram Hoetzenecker  1   7
Affiliations

Evidence of immunogenic cell death (ICD) and ICD-dependent dendritic cell activation induced by extracorporeal photopheresis in patients with leukaemic forms of cutaneous T-cell lymphoma

Angelika Lackner et al. Br J Dermatol. .

Abstract

Background: Despite novel therapeutic options, the long-term management of cutaneous T-cell lymphoma (CTCL) remains challenging. Extracorporeal photopheresis (ECP) is an immunomodulating photochemotherapy associated with higher overall survival when used for the treatment of leukaemic forms of CTCL. Its exact mode of action has not been fully elucidated. Immunogenic cell death (ICD) is pivotal in cancer immunotherapy, marked by the release of damage-associated molecular patterns that enhance dendritic cell (DC) maturation and cytotoxic T-lymphocyte responses.

Objectives: To explore ICD in patients with leukaemic forms of CTCL during ECP and its effect on DC activation.

Methods: We conducted in vitro studies with peripheral blood mononuclear cells (PBMCs) from healthy donors and ex vivo experiments with white blood cells (WBCs) from patients with leukaemic forms of CTCL undergoing ECP. We assessed cell viability, apoptosis and ICD markers [ATP, high mobility group box 1 protein (HMGB1), calreticulin] using flow cytometry, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Engulfment assays evaluated DC activation by ECP-treated CD4+ T cells.

Results: ECP-treated healthy PBMCs and WBCs from patients with leukaemic forms of CTCL showed a significant induction of ICD hallmarks, including ATP release, HMGB1 secretion and calreticulin surface exposure. In patients with leukaemic forms of CTCL, calreticulin exposure was mainly present in CD4+CD26- T cells, indicating greater ICD susceptibility of malignant T cells. ECP-treated CD4+ T cells were phagocytosed by DCs, a process that was found to be dependent on ICD signals.

Conclusions: ECP induces ICD in malignant T cells and, to a lesser extent, in healthy T cells, facilitates DC activation. These findings suggest that ECP enhances targeted immune responses against malignant T cells in leukaemic forms of CTCL, offering new insights into its therapeutic mechanisms and potential applications in cancer immunotherapy.

Plain language summary

Cutaneous T-cell lymphoma (‘CTCL’ for short) is a type of skin cancer that can also affect the blood. ‘Extracorporeal photopheresis’ (or ‘ECP’ for short) is used to treat people with a form of CTCL known as ‘leukaemic CTCL’. ECP takes white blood cells from a patient and treats them with a special light-sensitive drug. The cells are then exposed to ultraviolet A light (UVA) before being returned into the patient. While ECP is effective and safe, scientists still do not fully understand how it works. We investigated a process called ‘immunogenic cell death’ in patients with leukaemic forms of CTCL during ECP. We also looked at its effect on the activation of dendritic cells, a type of cell found in the immune system. We found that ECP triggers immunogenic cell death in patients with CTCL. This means that as the treated cancer cells die, they send signals to the immune system. This helps the immune system to recognize and attack more cancer cells. We also found that a specific type of cancerous T cell (called CD4+CD26– T cells) are very sensitive to this process. This suggests that ECP specifically targets tumour cells in patients with leukaemic CTCL, making it a promising treatment. In conclusion, our research shows how ECP helps the immune system fight CTCL. Future studies should focus on improving ECP treatment to make it even more effective for CTCL and possibly other T-cell cancers.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: The authors declare no conflict of interest.

Comment in

MeSH terms