Immune cell populations in the tumour environment following calcium electropora­tion for cutaneous metastasis: a histopathological study

Authors

  • Mille Vissing Centre for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde and Næstved, Næstved, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Sandra Sinius Pouplier Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark
  • Lars Munch Larsen Centre for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Næstved, Denmark
  • Stine Krog Frandsen Centre for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Næstved, Denmark
  • Alexey Lodin Centre for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Næstved, Denmark
  • Anne-Vibeke Lænkholm Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark
  • Julie Gehl Centre for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Roskilde and Næstved, Næstved, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; bDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

DOI:

https://doi.org/10.2340/1651-226X.2024.19462

Keywords:

Calcium electroporation, Cutaneous metastases, Histopathology, Tumour microenvironment, Clinical trial

Abstract

Background and Purpose: Calcium electroporation (CaEP) involves injecting calcium into tumour tissues and using electrical pulses to create membrane pores that induce cell death. This study assesses resultant immune responses and histopathological changes in patients with cutaneous metastases.

Patients/Materials and Methods: The aimed cohort comprised 24 patients with metastases exceeding 5 mm. Tumours were treated once with CaEP (day 0) or twice (day 28). Biopsies were performed on days 0 and 2, with additional samples on days 7, 28, 30, 35, 60, and 90 if multiple tumours were treated. The primary endpoint was the change in tumour-infiltrating lymphocytes (TILs) two days post-treatment, with secondary endpoints evaluating local and systemic immune responses via histopathological analysis of immune markers, necrosis, and inflammation.

Results: Seventeen patients, with metastases primarily from breast cancer (14 patients), but also lung cancer (1), melanoma (1), and urothelial cancer (1), completed the study. Of the 49 lesions treated, no significant changes in TIL count or PD-L1 expression were observed. However, there was substantial necrosis and a decrease in FOXP3-expression (p = 0.0025) noted, with a slight increase in CD4+ cells but no changes in CD3, CD8, or CD20 expressions. Notably, four patients showed reduced tumour invasiveness, including one case of an abscopal response.

Interpretation: This exploratory study indicates that CaEP can be an effective anti-tumour therapy potentially enhancing immunity. Significant necrosis and decreased regulatory lymphocytes were observed, although TIL count remained unchanged. Several patients exhibited clinical signs of immune response following treatment.

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Published

2024-05-28

How to Cite

Vissing, M., Sinius Pouplier, S., Munch Larsen, L., Krog Frandsen, S., Lodin, A., Lænkholm, A.-V., & Gehl, J. (2024). Immune cell populations in the tumour environment following calcium electropora­tion for cutaneous metastasis: a histopathological study. Acta Oncologica, 63(1), 398–410. https://doi.org/10.2340/1651-226X.2024.19462

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Vol. 63 (2024): Acta Oncologica

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Original article

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Copyright (c) 2023 Mille Vissing, Sandra Sinius Pouplier, Lars Munch Larsen, Stine Krog Frandsen, Alexey Lodin, Anne-Vibeke Lænkholm, Julie Gehl

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This work is licensed under a Creative Commons Attribution 4.0 International License.