The effect of calcium electroporation on viability, phenotype and function of melanoma conditioned macrophages

• Published in: Scientific reports 2020-11, Vol.10 (1), p.20645, Article 20645
• Main Authors: Tremble, Liam Friel, Heffron, Cynthia C. B. B., Forde, Patrick F.
• Format: Article
• Language: English
• Subjects: 631/67; 631/67/327; Animals; Apoptosis; Bleomycin; Bleomycin - pharmacology; Bone marrow; Bone Marrow - drug effects; Calcium; Calcium - pharmacology; Cell death; Cell Death - drug effects; Cell Line, Tumor; Cell Membrane - drug effects; Cell membranes; Cell Survival - drug effects; Chemotherapy; Electroporation; Electroporation - methods; Female; Humanities and Social Sciences; Immunity - drug effects; Immunogenicity; Lymphocytes T; Macrophages; Macrophages - drug effects; Melanoma; Melanoma, Experimental - diet therapy; Mice; Mice, Inbred C57BL; Mortality; multidisciplinary; Phenotype; Phenotypes; Science; Science (multidisciplinary); T-Lymphocytes - drug effects; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-77743-2

Electroporation in combination with chemotherapy is an established treatment used on solid malignancies that results in enhanced chemotherapeutic uptake. Recent advances have begun to transition to the use of non-toxic compounds, such as calcium, in lieu of chemotherapy, which can also induce tumour cell death. While the effect of treatment on tumour cell death has been well characterized and has been shown to induce an immunogenic form of cell death, the effect of treatment on intratumoural immune cells has not been investigated. Here we present data showing the effect of calcium electroporation on immune cells, using melanoma-conditioned bone marrow-derived macrophages. Similar to tumour cells, macrophage cell membranes are susceptible to poration following treatment and subsequently reseal. Macrophages are less susceptible to calcium electroporation induced cell death in comparison to B16F10 melanoma cells. However treatment with electroporation with or without bleomycin or calcium was shown to affect macrophage phenotype and function. Coculture of calcium electroporated macrophages revealed that both the capacity of macrophages to stimulate and direct T cell responses are affected following exposure to treatment. We conclude that calcium electroporation has the potential to boost the immunogenic capacity of exposed tumour associated macrophages, and further research is warranted to determine if calcium electroporation can be optimised to generate systemic anti-cancer immune responses.