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.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark.
Acta Oncol. 2024 May 28;63:398-410. doi: 10.2340/1651-226X.2024.19462.
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.
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.
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.
钙电穿孔(CaEP)涉及将钙离子注入肿瘤组织,并使用电脉冲在细胞膜上形成孔,从而诱导细胞死亡。本研究评估了钙电穿孔治疗皮肤转移瘤患者的免疫反应和组织病理学变化。
患者/材料与方法:本研究纳入了 24 名转移灶超过 5mm 的患者。肿瘤在第 0 天(CaEP 治疗日)或第 28 天(CaEP 治疗日)接受单次或两次治疗。在第 0 天和第 2 天进行活检,如果治疗了多个肿瘤,则在第 7、28、30、35、60 和 90 天进行额外的样本采集。主要终点是治疗后两天肿瘤浸润淋巴细胞(TIL)的变化,次要终点通过免疫标志物、坏死和炎症的组织病理学分析评估局部和全身免疫反应。
17 名患者(主要来自乳腺癌[14 名患者],还有 1 名来自肺癌、1 名来自黑色素瘤、1 名来自尿路上皮癌)完成了研究。在治疗的 49 个病灶中,TIL 计数或 PD-L1 表达没有显著变化。然而,观察到大量的坏死和 FOXP3 表达减少(p=0.0025),CD4+细胞略有增加,但 CD3、CD8 和 CD20 表达没有变化。值得注意的是,4 名患者的肿瘤侵袭性降低,包括 1 例发生了远隔效应。
这项探索性研究表明,CaEP 可能是一种有效的抗肿瘤治疗方法,能够增强免疫力。虽然 TIL 计数保持不变,但观察到明显的坏死和调节性淋巴细胞减少。治疗后,一些患者出现了免疫反应的临床迹象。