CancerResearch@UCC, University College Cork, Fourth floor, Western Gateway Building, Western Road, Cork, Ireland.
Department of Pathology, Cork University Hospital, Wilton, Cork, Ireland.
Sci Rep. 2020 Nov 26;10(1):20645. 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.
电穿孔联合化疗是一种已被证实的治疗实体恶性肿瘤的方法，可增强化疗药物的摄取。最近的进展开始转向使用无毒化合物，如钙，而不是化疗，也可以诱导肿瘤细胞死亡。虽然治疗对肿瘤细胞死亡的影响已经得到很好的描述，并已被证明能诱导免疫原性的细胞死亡，但治疗对肿瘤内免疫细胞的影响尚未被研究。在这里，我们展示了使用黑色素瘤条件培养基来源的巨噬细胞研究钙电穿孔对免疫细胞影响的数据。与肿瘤细胞类似，处理后巨噬细胞膜容易穿孔，随后重新封闭。与 B16F10 黑色素瘤细胞相比，巨噬细胞对钙电穿孔诱导的细胞死亡的敏感性较低。然而，用或不用博来霉素或钙进行电穿孔处理显示会影响巨噬细胞的表型和功能。共培养钙电穿孔的巨噬细胞表明，暴露于治疗后，巨噬细胞刺激和指导 T 细胞反应的能力都受到影响。我们得出结论，钙电穿孔有可能增强暴露的肿瘤相关巨噬细胞的免疫原性，需要进一步研究以确定钙电穿孔是否可以优化以产生全身抗肿瘤免疫反应。
