Pulsed electric field ablation as a candidate to enhance the anti-tumor immune response to immune checkpoint inhibitors

IF 9.1 1区 医学 Q1 ONCOLOGY
Blake M. Arciga , Dustin M. Walters , Eric T. Kimchi , Kevin F. Staveley-O’Carroll , Guangfu Li , Emma Teixeiro , Satyanarayana Rachagani , Jussuf T. Kaifi
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Abstract

Cancer ablation with pulsed electric fields (PEFs) involves the delivery of high-voltage, short-duration electrical pulses that destabilize tumor cells, leading to cellular death. Unlike most conventional ablation technologies, PEF ablation is non-thermal, allowing for safe and targeted energy delivery to the tumor without damaging surrounding tissue and critical structures. PEFs allow for specific dosing, predictable treatment zones, and preservation of the extracellular matrix and adjacent vascular tissues. Preclinical and preliminary clinical data suggest that PEF ablation may induce inflammatory changes in the tumor microenvironment (TME) that engage host innate and adaptive immune cells, stimulating an anti-tumor response. Specifically, PEF promotes local and systemic anti-tumor immune activation through immunogenic cell death and the release of damage-associated molecular patterns (DAMPs) and tumor antigens. This tumor-specific immune activation could potentially enhance response to immune checkpoint inhibitor (ICI) therapies. Furthermore, PEF ablation induces the formation of tertiary lymphoid structures (TLSs) in the TME, which are predictive biomarkers for responsiveness to ICI across several solid tumors. This combination of effects activates antigen-presenting cells and stimulates the effector T cell response, which is often inhibited in ICI-resistant cancer patients. In this review, the onco-immunological characteristics of PEF ablation are discussed, with special emphasis placed on the clinical potential of PEF ablation to induce anti-cancer immune responses and enhance responsiveness to ICI therapy in ablated and non-ablated (abscopal) tumors.
脉冲电场消融作为增强抗肿瘤免疫应答免疫检查点抑制剂的候选
脉冲电场(PEFs)的癌症消融涉及高压、短时间电脉冲的传递,这些电脉冲破坏肿瘤细胞的稳定,导致细胞死亡。与大多数传统消融技术不同,PEF消融是非热的,允许安全、有针对性地将能量输送到肿瘤,而不会损害周围组织和关键结构。pef允许特定的剂量,可预测的治疗区域,保存细胞外基质和邻近的血管组织。临床前和初步临床数据表明,PEF消融术可能诱导肿瘤微环境(TME)的炎症变化,这种炎症变化与宿主先天和适应性免疫细胞有关,从而刺激抗肿瘤反应。具体来说,PEF通过免疫原性细胞死亡和损伤相关分子模式(DAMPs)和肿瘤抗原的释放促进局部和全身抗肿瘤免疫激活。这种肿瘤特异性免疫激活可能潜在地增强对免疫检查点抑制剂(ICI)治疗的反应。此外,PEF消融诱导TME中三级淋巴样结构(TLSs)的形成,这是多种实体肿瘤对ICI反应性的预测性生物标志物。这种组合效应激活抗原呈递细胞并刺激效应T细胞反应,而这种反应通常在ici耐药的癌症患者中被抑制。在这篇综述中,我们讨论了PEF消融的肿瘤免疫学特征,特别强调了PEF消融在消融和非消融肿瘤中诱导抗癌免疫反应和增强对ICI治疗的反应性的临床潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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