Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field

Jianpeng Liu, Xinhua Chen, Shusen Zheng

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PDF(309 KB)
Front. Med. ›› 2021, Vol. 15 ›› Issue (2) : 170-177. DOI: 10.1007/s11684-020-0747-z
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Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field

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Abstract

Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.

Keywords

nanosecond pulsed electric fields (nsPEF) / hepatocellular carcinoma (HCC) / immune response / recurrence / metastasis

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Jianpeng Liu, Xinhua Chen, Shusen Zheng. Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric field. Front. Med., 2021, 15(2): 170‒177 https://doi.org/10.1007/s11684-020-0747-z

References

[1]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87–108
CrossRef Pubmed Google scholar
[2]
Fitzmorris P, Shoreibah M, Anand BS, Singal AK. Management of hepatocellular carcinoma. J Cancer Res Clin Oncol 2015; 141(5): 861–876
CrossRef Pubmed Google scholar
[3]
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334(11): 693–699
CrossRef Pubmed Google scholar
[4]
Nault JC, Sutter O, Nahon P, Ganne-Carrié N, Séror O. Percutaneous treatment of hepatocellular carcinoma: state of the art and innovations. J Hepatol 2018; 68(4): 783–797
CrossRef Pubmed Google scholar
[5]
Wu F, Wang ZB, Chen WZ, Wang W, Gui Y, Zhang M, Zheng G, Zhou Y, Xu G, Li M, Zhang C, Ye H, Feng R. Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. Ultrason Sonochem 2004; 11(3-4): 149–154
CrossRef Pubmed Google scholar
[6]
Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006; 243(3): 321–328
CrossRef Pubmed Google scholar
[7]
Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, Rossi S. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology 2008; 47(1): 82–89
CrossRef Pubmed Google scholar
[8]
Künzli BM, Abitabile P, Maurer CA. Radiofrequency ablation of liver tumors: actual limitations and potential solutions in the future. World J Hepatol 2011; 3(1): 8–14
CrossRef Pubmed Google scholar
[9]
Pliquett U, Nuccitelli R. Measurement and simulation of Joule heating during treatment of B-16 melanoma tumors in mice with nanosecond pulsed electric fields. Bioelectrochemistry 2014; 100: 62–68
CrossRef Pubmed Google scholar
[10]
Beebe SJ, Sain NM, Ren W. Induction of cell death mechanisms and apoptosis by nanosecond pulsed electric fields (nsPEFs). Cells 2013; 2(1): 136–162
CrossRef Pubmed Google scholar
[11]
Nuccitelli R, McDaniel A, Anand S, Cha J, Mallon Z, Berridge JC, Uecker D. Nano-pulse stimulation is a physical modality that can trigger immunogenic tumor cell death. J Immunother Cancer 2017; 5(1): 32
CrossRef Pubmed Google scholar
[12]
Nuccitelli R, Lui K, Kreis M, Athos B, Nuccitelli P. Nanosecond pulsed electric field stimulation of reactive oxygen species in human pancreatic cancer cells is Ca2+-dependent. Biochem Biophys Res Commun 2013; 435(4): 580–585
CrossRef Pubmed Google scholar
[13]
He L, Xiao D, Feng J, Yao C, Tang L. Induction of apoptosis of liver cancer cells by nanosecond pulsed electric fields (nsPEFs). Med Oncol 2017; 34(2): 24
CrossRef Pubmed Google scholar
[14]
Chen X, Yin S, Hu C, Chen X, Jiang K, Ye S, Feng X, Fan S, Xie H, Zhou L, Zheng S. Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo. PLoS One 2014; 9(1): e86421
CrossRef Pubmed Google scholar
[15]
Chen R, Sain NM, Harlow KT, Chen YJ, Shires PK, Heller R, Beebe SJ. A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields. Eur J Cancer 2014; 50(15): 2705–2713
CrossRef Pubmed Google scholar
[16]
Nuccitelli R, Tran K, Lui K, Huynh J, Athos B, Kreis M, Nuccitelli P, De Fabo EC. Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response. Pigment Cell Melanoma Res 2012; 25(5): 618–629
CrossRef Pubmed Google scholar
[17]
Guo S, Burcus NI, Hornef J, Jing Y, Jiang C, Heller R, Beebe SJ. Nano-pulse stimulation for the treatment of pancreatic cancer and the changes in immune profile. Cancers (Basel) 2018; 10(7): 217PMID: 29954062
CrossRef Google scholar
[18]
Guo S, Jing Y, Burcus NI, Lassiter BP, Tanaz R, Heller R, Beebe SJ. Nano-pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases. Int J Cancer 2018; 142(3): 629–640
CrossRef Pubmed Google scholar
[19]
Nuccitelli R, Wood R, Kreis M, Athos B, Huynh J, Lui K, Nuccitelli P, Epstein EH Jr. First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method. Exp Dermatol 2014; 23(2): 135–137
CrossRef Pubmed Google scholar
[20]
Chen X, Chen Y, Jiang J, Wu L, Yin S, Miao X, Swanson RJ, Zheng S. Nano-pulse stimulation (NPS) ablate tumors and inhibit lung metastasis on both canine spontaneous osteosarcoma and murine transplanted hepatocellular carcinoma with high metastatic potential. Oncotarget 2017; 8(27): 44032–44039
CrossRef Pubmed Google scholar
[21]
Yin S, Chen X, Hu C, Zhang X, Hu Z, Yu J, Feng X, Jiang K, Ye S, Shen K, Xie H, Zhou L, James Swanson R, Zheng S. Nanosecond pulsed electric field (nsPEF) treatment for hepatocellular carcinoma: a novel locoregional ablation decreasing lung metastasis. Cancer Lett 2014; 346(2): 285–291
CrossRef Pubmed Google scholar
[22]
Chen X, Zhuang J, Kolb JF, Schoenbach KH, Beebe SJ. Long term survival of mice with hepatocellular carcinoma after pulse power ablation with nanosecond pulsed electric fields. Technol Cancer Res Treat 2012; 11(1): 83–93
CrossRef Pubmed Google scholar
[23]
Schoenbach KH, Joshi R, Kolb J, Buescher S, Beebe S. Subcellular effects of nanosecond electrical pulses. Conf Proc IEEE Eng Med Biol Soc 2004; 7: 5447–5450
Pubmed
[24]
Nuccitelli R, Pliquett U, Chen X, Ford W, James Swanson R, Beebe SJ, Kolb JF, Schoenbach KH. Nanosecond pulsed electric fields cause melanomas to self-destruct. Biochem Biophys Res Commun 2006; 343(2): 351–360
CrossRef Pubmed Google scholar
[25]
Nuccitelli R, Chen X, Pakhomov AG, Baldwin WH, Sheikh S, Pomicter JL, Ren W, Osgood C, Swanson RJ, Kolb JF, Beebe SJ, Schoenbach KH. A new pulsed electric field therapy for melanoma disrupts the tumor’s blood supply and causes complete remission without recurrence. Int J Cancer 2009; 125(2): 438–445
CrossRef Pubmed Google scholar
[26]
Nuccitelli R, Tran K, Sheikh S, Athos B, Kreis M, Nuccitelli P. Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self-destruct with a single treatment. Int J Cancer 2010; 127(7): 1727–1736
CrossRef Pubmed Google scholar
[27]
Vernier PT, Sun Y, Marcu L, Salemi S, Craft CM, Gundersen MA. Calcium bursts induced by nanosecond electric pulses. Biochem Biophys Res Commun 2003; 310(2): 286–295
CrossRef Pubmed Google scholar
[28]
Pakhomova ON, Khorokhorina VA, Bowman AM, Rodaitė-Riševičienė R, Saulis G, Xiao S, Pakhomov AG. Oxidative effects of nanosecond pulsed electric field exposure in cells and cell-free media. Arch Biochem Biophys 2012; 527(1): 55–64 doi:10.1016/j.abb.2012.08.004
Pubmed
[29]
Adkins I, Fucikova J, Garg AD, Agostinis P, Špíšek R. Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy. OncoImmunology 2015; 3(12): e968434
CrossRef Pubmed Google scholar
[30]
Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 2012; 12(12): 860–875
CrossRef Pubmed Google scholar
[31]
Mbeunkui F, Johann DJ Jr. Cancer and the tumor microenvironment: a review of an essential relationship. Cancer Chemother Pharmacol 2009; 63(4): 571–582
CrossRef Pubmed Google scholar
[32]
Leonardi GC, Candido S, Cervello M, Nicolosi D, Raiti F, Travali S, Spandidos DA, Libra M. The tumor microenvironment in hepatocellular carcinoma. Int J Oncol 2012; 40(6): 1733–1747
Pubmed
[33]
Baglieri J, Brenner DA, Kisseleva T. The role of fibrosis and liver-associated fibroblasts in the pathogenesis of hepatocellular carcinoma. Int J Mol Sci 2019; 20(7): 1723
CrossRef Pubmed Google scholar
[34]
Critelli R, Milosa F, Faillaci F, Condello R, Turola E, Marzi L, Lei B, Dituri F, Andreani S. Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study. Cell Death Dis 2017; 8(8): e3017PMID: 28837142
CrossRef Google scholar
[35]
Wang Y, Takeishi K, Li Z, Cervantes-Alvarez E, Collin de l’Hortet A, Guzman-Lepe J, Cui X, Zhu J. Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks. Organogenesis 2017; 13(3): 83–94
CrossRef Pubmed Google scholar
[36]
Smyth MJ, Ngiow SF, Ribas A, Teng MW. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol 2016; 13(3): 143–158
CrossRef Pubmed Google scholar
[37]
Gao C, Zhang X, Chen J, Zhao J, Liu Y, Zhang J, Wang J. Utilizing the nanosecond pulse technique to improve antigen intracellular delivery and presentation to treat tongue squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 2018; 23(3): e344–e350
CrossRef Pubmed Google scholar
[38]
Skeate JG, Da Silva DM, Chavez-Juan E, Anand S, Nuccitelli R, Kast WM. Nano-pulse stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response. PLoS One 2018; 13(1): e0191311
CrossRef Pubmed Google scholar
[39]
Lassiter BP, Guo S, Beebe SJ. Nano-pulse stimulation ablates orthotopic rat hepatocellular carcinoma and induces innate and adaptive memory immune mechanisms that prevent recurrence. Cancers (Basel) 2018; 10(3): 69
Pubmed
[40]
Nuccitelli R, Berridge JC, Mallon Z, Kreis M, Athos B, Nuccitelli P. Nanoelectroablation of murine tumors triggers a CD8-dependent inhibition of secondary tumor growth. PLoS One 2015; 10(7): e0134364
CrossRef Pubmed Google scholar
[41]
Blachère NE, Darnell RB, Albert ML. Apoptotic cells deliver processed antigen to dendritic cells for cross-presentation. PLoS Biol 2005; 3(6): e185
CrossRef Pubmed Google scholar
[42]
Dromi SA, Walsh MP, Herby S, Traughber B, Xie J, Sharma KV, Sekhar KP, Luk A, Liewehr DJ, Dreher MR, Fry TJ, Wood BJ. Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology 2009; 251(1): 58–66
CrossRef Pubmed Google scholar
[43]
Mizukoshi E, Yamashita T, Arai K, Sunagozaka H, Ueda T, Arihara F, Kagaya T, Yamashita T, Fushimi K, Kaneko S. Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma. Hepatology 2013; 57(4): 1448–1457
CrossRef Pubmed Google scholar
[44]
Ahmad F, Gravante G, Bhardwaj N, Strickland A, Basit R, West K, Sorge R, Dennison AR, Lloyd DM. Changes in interleukin-1b and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections. Am J Surg 2010; 200(4): 500–506
CrossRef Pubmed Google scholar
[45]
Sabel MS. Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology 2009; 58(1): 1–11PMID:19007768
CrossRef Google scholar
[46]
Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations- boosting the anticancer immune response. J Immunother Cancer 2017; 5(1): 78
CrossRef Pubmed Google scholar

Acknowledgements

This work was supported by National S&T Major Project (No. 2018ZX10301201) and Innovative Research Groups of National Natural Science Foundation of China (No. 81721091). The authors thank Dr. Lin Zhou, Dr. Haiyang Xie, Danjing Guo, and Liangjie Hong from Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health for their comments.

Compliance with ethics guidelines

Jianpeng Liu, Xinhua Chen, and Shusen Zheng declare that they have no financial conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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