研究动态
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钙电穿孔皮肤转移后肿瘤环境中的免疫细胞群:组织病理学研究。

Immune cell populations in the tumour environment following calcium electropora-tion for cutaneous metastasis: a histopathological study.

发表日期:2024 May 28
作者: Mille Vissing, Sandra Sinius Pouplier, Lars Munch Larsen, Stine Krog Frandsen, Alexey Lodin, Anne-Vibeke Lænkholm, Julie Gehl
来源: Cell Death & Disease

摘要:

钙电穿孔 (CaEP) 涉及将钙注射到肿瘤组织中,并使用电脉冲形成膜孔,从而诱导细胞死亡。本研究评估了皮肤转移患者的免疫反应和组织病理学变化。目标队列包括 24 名转移超过 5 毫米的患者。用 CaEP 治疗肿瘤一次(第 0 天)或两次(第 28 天)。在第 0 天和第 2 天进行活检,如果治疗多个肿瘤,则在第 7、28、30、35、60 和 90 天进行额外的样本。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记物、坏死和炎症的组织病理学分析来评估局部和全身免疫反应。 17 名患者,主要来自乳腺癌转移(14 名患者)、肺癌 (1)、黑色素瘤 (1) 和尿路上皮癌 (1) 完成了这项研究。在治疗的 49 个病灶中,未观察到 TIL 计数或 PD-L1 表达的显着变化。然而,注意到存在大量坏死和 FOXP3 表达减少 (p = 0.0025),CD4 细胞略有增加,但 CD3、CD8 或 CD20 表达没有变化。值得注意的是,四名患者表现出肿瘤侵袭性降低,其中包括一名远隔反应病例。这项探索性研究表明,CaEP 可以成为一种有效的抗肿瘤疗法,有可能增强免疫力。尽管 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。一些患者在治疗后表现出免疫反应的临床症状。
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.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.