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. 2023 May 6;24(9):8335.
doi: 10.3390/ijms24098335.

Electrochemotherapy of Melanoma Cutaneous Metastases in Organ Transplant Recipients: A Systematic Review of Preclinical and Clinical Studies

Sara Milicevic  1   2 , Maja Cemazar  1   3 , Andreja Klevisar Ivancic  1 , Gorana Gasljevic  1 , Masa Bosnjak  1   4 , Gregor Sersa  1   5 , Barbara Peric  1   2
Affiliations

Electrochemotherapy of Melanoma Cutaneous Metastases in Organ Transplant Recipients: A Systematic Review of Preclinical and Clinical Studies

Sara Milicevic et al. Int J Mol Sci. .

Abstract

Cutaneous melanoma is a highly aggressive form of skin cancer. The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of advanced melanoma, led to durable responses, and improved overall survival. However, the success of ICIs in melanoma treatment is influenced by the tumor microenvironment (TME) which plays a critical role in regulating the immune response to the tumor. Understanding the mechanisms underlying this interaction is crucial to optimizing the efficiency of ICIs. Electrochemotherapy (ECT) has been shown to enhance the efficacy of ICIs in melanoma treatment by inducing tumor cell death and facilitating the release of tumor antigens which can subsequently be recognized and targeted by the immune system. Moreover, ECT has been reported to modulate the TME, leading to increased infiltration of immune cells and a more favorable immunological profile. In this review, we summarize the available knowledge of changes in TME after ECT of melanoma cutaneous metastasis and highlight the differences in tumor-infiltrating immune cells between immunocompetent and immunosuppressed organisms. In addition, we showed that ECT can be an effective and safe procedure for organ transplant recipients. Furthermore, repeated ECT may enhance immune activation and probably induce a bystander effect by trained immunity.

Keywords: cutaneous melanoma; electrochemotherapy; immune checkpoint inhibitors; immunosuppression; tumor microenvironment.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1
Figure 1
Treatment course of in-transit melanoma metastases; (A) 1st ECT; (B) 2nd ECT; (C) 1 month after the 2nd ECT; (D) 3rd ECT; (E) 4th ECT; (F) 1 month after the 4th ECT.
Figure 2
Figure 2
Histopathology of excised vital in-transit CM nodule 5 months after 4th ECT; (A) H&E, 2×; (B) H & E, 10×; (C) CD3, 20×; (D) CD8, 20×; (E) CD4, 20×; lymphocytes indicated by arrows; (F) CD56, 20×; lymphocytes indicated by arrows; (G) FoxP3, 20×; (H) CD163, 20×.
Figure 3
Figure 3
Histopathology of excised completely regressed pretreated in-transit CM nodule 5 months after the 4th ECT, H&E staining, 2×.
See this image and copyright information in PMC

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