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将电磁癌症应激与免疫疗法相结合:一种治疗模式。

Integrating electromagnetic cancer stress with immunotherapy: a therapeutic paradigm.

作者信息

Fuster Mark M

机构信息

Research Service, VA San Diego Healthcare System, San Diego, CA, United States.

Pulmonary & Critical Care Division, University of California, San Diego, San Diego, CA, United States.

出版信息

Front Oncol. 2024 Aug 6;14:1417621. doi: 10.3389/fonc.2024.1417621. eCollection 2024.


DOI:10.3389/fonc.2024.1417621
PMID:39165679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11333800/
Abstract

An array of published cell-based and small animal studies have demonstrated a variety of exposures of cancer cells or experimental carcinomas to electromagnetic (EM) wave platforms that are non-ionizing and non-thermal. Overall effects appear to be inhibitory, inducing cancer cell stress or death as well as inhibition in tumor growth in experimental models. A variety of physical input variables, including discrete frequencies, amplitudes, and exposure times, have been tested, but drawing methodologic rationale and mechanistic conclusions across studies is challenging. Nevertheless, outputs such as tumor cytotoxicity, apoptosis, tumor membrane electroporation and leak, and reactive oxygen species generation are intriguing. Early EM platforms in humans employ pulsed electric fields applied either externally or using interventional tumor contact to induce tumor cell electroporation with stromal, vascular, and immunologic sparing. It is also possible that direct or external exposures to non-thermal EM waves or pulsed magnetic fields may generate electromotive forces to engage with unique tumor cell properties, including tumor glycocalyx to induce carcinoma membrane disruption and stress, providing novel avenues to augment tumor antigen release, cross-presentation by tumor-resident immune cells, and anti-tumor immunity. Integration with existing checkpoint inhibitor strategies to boost immunotherapeutic effects in carcinomas may also emerge as a broadly effective strategy, but little has been considered or tested in this area. Unlike the use of chemo/radiation and/or targeted therapies in cancer, EM platforms may allow for the survival of tumor-associated immunologic cells, including naïve and sensitized anti-tumor T cells. Moreover, EM-induced cancer cell stress and apoptosis may potentiate endogenous tumor antigen-specific anti-tumor immunity. Clinical studies examining a few of these combined EM-platform approaches are in their infancy, and a greater thrust in research (including basic, clinical, and translational work) in understanding how EM platforms may integrate with immunotherapy will be critical in driving advances in cancer outcomes under this promising combination.

摘要

一系列已发表的基于细胞和小动物的研究表明,癌细胞或实验性癌在非电离、非热的电磁波平台上有多种暴露情况。总体效果似乎具有抑制作用,可诱导癌细胞应激或死亡,并在实验模型中抑制肿瘤生长。已经测试了各种物理输入变量,包括离散频率、振幅和暴露时间,但跨研究得出方法学原理和机制结论具有挑战性。然而,诸如肿瘤细胞毒性、细胞凋亡、肿瘤膜电穿孔和渗漏以及活性氧生成等结果很有趣。早期用于人类的电磁波平台采用外部施加的脉冲电场或通过介入性肿瘤接触来诱导肿瘤细胞电穿孔,同时保留基质、血管和免疫功能。直接或外部暴露于非热电磁波或脉冲磁场也有可能产生电动势,以作用于独特的肿瘤细胞特性,包括肿瘤糖萼,从而诱导癌细胞膜破坏和应激,为增加肿瘤抗原释放、肿瘤驻留免疫细胞的交叉呈递和抗肿瘤免疫提供新途径。与现有的检查点抑制剂策略相结合以增强癌症免疫治疗效果也可能成为一种广泛有效的策略,但在这一领域几乎没有得到考虑或测试。与在癌症中使用化学疗法/放射疗法和/或靶向疗法不同,电磁波平台可能允许肿瘤相关免疫细胞存活,包括未致敏和致敏的抗肿瘤T细胞。此外,电磁波诱导的癌细胞应激和凋亡可能增强内源性肿瘤抗原特异性抗肿瘤免疫。研究这些联合电磁波平台方法中的少数几种的临床研究尚处于起步阶段,加大研究力度(包括基础、临床和转化研究)以了解电磁波平台如何与免疫疗法整合,对于推动这种有前景的联合疗法在癌症治疗方面取得进展至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/4485854c2f77/fonc-14-1417621-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/6dab5edb0a98/fonc-14-1417621-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/671f4a1b464f/fonc-14-1417621-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/ced8e6366526/fonc-14-1417621-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/4485854c2f77/fonc-14-1417621-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/6dab5edb0a98/fonc-14-1417621-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/671f4a1b464f/fonc-14-1417621-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/ced8e6366526/fonc-14-1417621-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a41/11333800/4485854c2f77/fonc-14-1417621-g004.jpg

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