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usEPs as a Possible Immunotherapy

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Ultrashort Electric Pulse Effects in Biology and Medicine

Part of the book series: Series in BioEngineering ((SERBIOENG))

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Abstract

That usEPs could ablate tumors was a significant finding in the use of this technology for cancer therapy. The finding that usEPs could also induce immunity was a bonus for this treatment as possible immunotherapy. However, the data to support this immune induction by usEPs had several different sets of suggestive evidence. One approach showed slower tumor growth in immunocompetent mice vs. growth in immunodeficient mice. A second approach showed the slower growth of a secondary tumor after ablation of a primary tumor, suggesting that the primary treatment caused an immune response that slowed secondary tumor growth. The presence of CD4+ T-cells in the primary treated tumors and CD4+ cells in the untreated secondary tumor was used as evidence. However, the CD4+ cells require further characterization to differentiate CD4+  CD25+ Foxp3+ T-regulatory immunosuppressor cells (Tregs) from CD4+ CD44+ with the presence or absence of CD62L+ as T-central or T effector memory cells, respectively. The strongest evidence for usEP-induced immunity indicated the complete absence of secondary tumor growth after primary tumor treatment. Such responses were present in cancer models in the ectopic mouse liver, orthotopic mouse breast, and rat liver cancers. The absence of secondary tumor growth is called vaccine effects or in situ vaccination. Thus, the treatment of the primary tumor induces immunity and vaccinates the animals by the usEP treatment. The latter two cancers exhibited early decreases in immunosuppressor Tregs and myeloid-derived suppressor cells (MDSC), which resolve suppression of immune responses, and increases in dendritic cells (DCs) in the TME that could identify antigens and induced immunity. The rat liver cancer model also showed activation of the innate immune natural killer (NK) cells with specific activation markers in its TME and the presence of effector and central memory cells in the mouse breast and rat liver (TME), which were cytotoxic. An ectopic mouse pancreatic cancer model that did not show a vaccine effect failed to show a decrease in Tregs and MDSC in the TME and blood and did not show activated T-cells, suggesting immunosuppression prevented an immune response. Continued studies will determine immunity, cell death mechanisms, and ICD factors (calreticulin, ATP, and HMGB1) in other immunogenic cancer models.

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References

  • Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355

    Article  Google Scholar 

  • Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ (2001) High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192(4):565–570

    Article  Google Scholar 

  • Badovinac VP, Porter BB, Harty JT (2002) Programmed contraction of CD8(+) T cells after infection. Nat Immunol 3(7):619–626

    Article  Google Scholar 

  • Badovinac VP, Messingham KA, Jabbari A, Haring JS, Harty JT (2005) Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination. Nat Med 11(7):748–756

    Article  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  Google Scholar 

  • Bartel DP (2018) Metazoan microRNAs. Cell 173(1):20–51

    Article  Google Scholar 

  • Barry M, Heibein JA, Pinkoski MJ, Lee SF, Moyer RW, Green DR, Bleackley RC (2000) Mol Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid. Cell Biol 20(11):3781–3794

    Google Scholar 

  • Beebe SJ, Fox PM, Rec LH, Buescher ES, Somers K, Schoenbach KH (2002) Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition. IEEE Trans Plasma Sci 30:286–292

    Article  Google Scholar 

  • Beebe SJ, Fox PM, Rec LJ, Willis EL, Schoenbach KH (2003) Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J 17:1493–2145

    Article  Google Scholar 

  • Beebe SJ, Ford WE, Ren W, Chen X (2011) Pulse power ablation of melanoma with nanosecond pulsed electric fields. In: Morton R (ed) Treatment of metastatic melanoma. In Tech Croatia, pp 231–268. ISBN 978-953-307-574-7. https://doi.org/10.5772/22850

  • Beebe SJ, Lassiter BP, Guo S (2018) Nanopulse stimulation (NPS) induces tumor ablation and immunity in orthotopic 4T1 mouse breast cancer: a review. Cancers (basel) 10(4):97

    Article  Google Scholar 

  • Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, Schietinger A, Schumacher TN, Schwartzberg PL, Sharpe AH, Speiser DE, Wherry EJ, Youngblood BA, Zehn D (2019) Defining ‘T cell exhaustion'. Nat Rev Immunol 11:665–674

    Google Scholar 

  • Boraschi D, Italiani P (2018) Innate immune memory: time for adopting a correct terminology. Front Immunol 9:799

    Google Scholar 

  • Bunt SK, Sinha P, Clements VK et al (2006) Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol 176:284–290

    Article  Google Scholar 

  • Casares N, Pequignot MO, Tesniere A, Ghiringhelli F, Roux S, Chaput N, Schmitt E, Hamai A, Hervas-Stubbs S, Obeid M, Coutant F, Métivier D, Pichard E, Aucouturier P, Pierron G, Garrido C, Zitvogel L, Kroemer G (2005) Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 202(12):1691–1701

    Article  Google Scholar 

  • Cerwenka A, Lanier LL (2016) Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol 16(2):112–123

    Google Scholar 

  • Chai LF, Prince E, Pillarisetty VG, Katz SC (2020) Challenges in assessing solid tumor responses to immunotherapy. Cancer Gene Ther 27(7–8):528–538

    Article  Google Scholar 

  • Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ (2007) Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 27(4):635–646

    Article  Google Scholar 

  • Chen R, Sain NM, Harlow KT, Chen YJ, Shires PK, Heller R, Beebe SJ (2014) A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields. Eur J Cancer 50(15):2705–2713

    Article  Google Scholar 

  • Chen X, Kolb JF, Swanson RJ, Schoenbach KH, Beebe SJ (2010) Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields. Pigment Cell Melanoma Res 23:554–563

    Article  Google Scholar 

  • Chen X, Zhuang J, Kolb JF, Schoenbach KH, Beebe SJ (2012) Long term survival of mice with hepatocellular carcinoma after pulse power ablation with nanosecond pulsed electric fields. Technol Cancer Res Treat 11:83–93

    Article  Google Scholar 

  • Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M (2012) Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol 13(9):832–842

    Article  Google Scholar 

  • Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461(7261):282–286

    Article  Google Scholar 

  • Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391(6662):43–50

    Article  Google Scholar 

  • Escors D (2014) Tumour immunogenicity, antigen presentation and immunological barriers in cancer immunotherapy. New J Sci 2014:734515

    Article  Google Scholar 

  • Fergusson JR, Fleming VM, Klenerman P (2011) CD161-Expressing hHuman T cells. Front Immunol 2:36

    Article  Google Scholar 

  • Fergusson JR, Smith KE, Fleming VM, Rajoriya N, Newell EW, Simmons R, Marchi E, Björkander S, Kang YH, Swadling L, Kurioka A, Sahgal N, Lockstone H, Baban D, Freeman GJ, Sverremark-Ekström E, Davis MM, Davenport MP, Venturi V, Ussher JE, Willberg CB, Klenerman P (2014) CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages. Cell Rep 9(3):1075–1088

    Article  Google Scholar 

  • Gabrielli S, Ortolani C, Del Zotto G, Luchetti F, Canonico B, Buccella F, Artico M, Papa S, Zamai L (2016) The memories of NK cells: innate-adaptive immune intrinsic crosstalk. J Immunol Res 2016:1376595

    Article  Google Scholar 

  • Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174

    Article  Google Scholar 

  • Gamrekelashvili J, Ormandy LA, Heimesaat MM, Kirschning CJ, Manns MP, Korangy F, Greten TF (2012) Primary sterile necrotic cells fail to cross-prime CD8(+) T cells. Oncoimmunology 1(7):1017–1026

    Article  Google Scholar 

  • Gardiner CM, Finlay DK (2017) What fuels natural killers? metabolism and NK cell responses. Front Immunol 8:367

    Article  Google Scholar 

  • Garg AD, Krysko DV, Vandenabeele P, Agostinis P (2012) The emergence of phox-ER stress induced immunogenic apoptosis. Oncoimmunology 1(5):786–788

    Article  Google Scholar 

  • Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W (1995) Schulte-Hermann R In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 21(5):1465–1468

    Google Scholar 

  • Green DR, Ferguson T, Zitvogel L, Kroemer G (2009) Immunogenic and tolerogenic cell death. Nat Rev Immunol 9:353–363

    Google Scholar 

  • Guo S, Jing Y, Burcus NI, Lassiter BP, Tanaz R, Heller R, Beebe SJ (2018) Nano-pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases. Int J Cancer 142(3):629–640

    Article  Google Scholar 

  • Guo ZS, Liu Z, Bartlett DL (2014) Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol 4:74

    Google Scholar 

  • Haabeth OA, Tveita AA, Fauskanger M, Schjesvold F, Lorvik KB, Hofgaard PO, Omholt H, Munthe LA, Dembic Z, Corthay A, Bogen B (2014) How do CD4(+) T cells detect and eliminate tumor cells that either lack or express MHC class II molecules? Front Immunol 5:174

    Article  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  Google Scholar 

  • Hazenberg MD, Spits H (2014) Human innate lymphoid cells. Blood 124(5):700–709

    Article  Google Scholar 

  • Hou W, Zhang Q, Yan Z, Chen R, Zeh HJ III, Kang R, Lotze MT, Tang D (2013) Strange attractors: DAMPs and autophagy link tumor cell death and immunity. Cell Death Dis 4(12):e966

    Article  Google Scholar 

  • Inoue H, Tani K (2014) Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell Death Differ 21:39–49

    Article  Google Scholar 

  • Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72

    Article  Google Scholar 

  • Krysko DV, D’Herde K, Vandenabeele P (2006) Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11(10):1709–1726

    Article  Google Scholar 

  • Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Martin MD, Badovinac VP (2018) Defining memory CD8 T cell. Front Immunol 9:2692

    Google Scholar 

  • Kazama H, Ricci JE, Herndon JM, Hoppe G, Green DR, Ferguson TA (2008) Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29(1):21–32

    Article  Google Scholar 

  • Kepp O, Galluzzi L, Martins I, Schlemmer F, Adjemian S, Michaud M, Sukkurwala AQ, Menger L, Zitvogel L, Kroemer G (2011) Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 30(1):61–69

    Article  Google Scholar 

  • Koo GB, Morgan MJ, Lee DG, Kim WJ, Yoon JH, Koo JS, Kim SI, Kim SJ, Son MK, Hong SS, Levy JM, Pollyea DA, Jordan CT, Yan P, Frankhouser D, Nicolet D, Maharry K, Marcucci G, Choi KS, Cho H, Thorburn A, Kim YS (2015) Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics. Cell Res 25:707–725

    Article  Google Scholar 

  • Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P (2012) Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer 12:860–875

    Article  Google Scholar 

  • Lanier LL (2015) NKG2D Receptor and its ligands in host defense. Cancer Immunol Res 3(6):575–582

    Article  Google Scholar 

  • Lassiter BP, Guo S, Beebe SJ (2018) Nano-pulse stimulation ablates orthotopic rat hepatocellular carcinoma and induces innate and adaptive memory immune mechanisms that prevent recurrence. Cancers (basel) 10(3):69

    Article  Google Scholar 

  • Lieberman J (2010) Anatomy of a murder: how cytotoxic T cells and NK cells are activated, develop, and eliminate their targets. Immunol Rev 235:5–9

    Article  Google Scholar 

  • Ljunggren HG, Kärre K (1990) In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today 11(7):237–244

    Article  Google Scholar 

  • Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC (2003) Granzyme B: a natural born killer. Immunol Rev 193:31–38

    Article  Google Scholar 

  • Luckey CJ, Bhattacharya D, Goldrath AW, Weissman IL, Benoist C, Mathis D (2006) Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci USA 103(9):3304–3309

    Article  Google Scholar 

  • Maggi L, Santarlasci V, Capone M, Peired A, Frosali F, Crome SQ, Querci V, Fambrini M, Liotta F, Levings MK, Maggi E, Cosmi L, Romagnani S, Annunziato F (2010) CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC. Eur J Immunol 40(8):2174–2181

    Article  Google Scholar 

  • Matassov D, Kagan T, Leblanc J, Sikorska M, Zakeri Z (2004) Measurement of apoptosis by DNA fragmentation. Methods Mol Biol 282:1–17

    Google Scholar 

  • Martin MD, Badovinac VP (2018) Defining Memory CD8 T Cell. Front Immunol 9:2692

    Article  Google Scholar 

  • Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec M, Mignot G, Rello-Varona S, Tailler M, Menger L, Vacchelli E, Galluzzi L, Ghiringhelli F, di Virgilio F, Zitvogel L, Kroemer G (2011) Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334(6062):1573–1577

    Article  Google Scholar 

  • Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  Google Scholar 

  • Moretta A, Marcenaro E, Parolini S, Ferlazzo G, Moretta L (2008) NK cells at the interface between innate and adaptive immunity. Cell Death Differ 15(2):226–233

    Google Scholar 

  • Morotomi-Yano K, Oyadomari S, Akiyama H, Yano K (2012) Nanosecond pulsed electric fields act as a novel cellular stress that induces translational suppression accompanied by eIF2α phosphorylation and 4E-BP1 dephosphorylation. Exp Cell Res. 318(14):1733–1744

    Article  Google Scholar 

  • Morrison MJ, Pallares G, Patel HK, Kroemer G1, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72

    Google Scholar 

  • Murdoch C, Muthana M, Coffelt SB et al (2008) The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 8:618–631

    Article  Google Scholar 

  • Netea MG, Joosten LA, Latz E, Mills K, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ (2016) Trained immunity: a program of innate immune memory in health and disease. Science 352:aaf1098

    Google Scholar 

  • Nuccitelli R, Tran K, Lui K, Huynh J, Athos B, Kreis M, Nuccitelli P, De Fabo EC (2012) Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response. Pigment Cell Melanoma Res 25(5):618–629

    Article  Google Scholar 

  • Nuccitelli R, McDaniel A, Anand S, Cha J, Mallon Z, Berridge JC, Uecker D (2017) Nano-Pulse Stimulation is a physical modality that can trigger immunogenic tumor cell death. J Immunother Cancer 5:32

    Article  Google Scholar 

  • Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Métivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13(1):54–61

    Article  Google Scholar 

  • O’Brien KL, Finlay DK (2019) Immunometabolism and natural killer cell responses. Nat Rev Immunol 19(5):282–290

    Article  Google Scholar 

  • Panaretakis T, Joza N, Modjtahedi N, Tesniere A, Vitale I, Durchschlag M, Fimia GM, Kepp O, Piacentini M, Froehlich KU, van Endert P, Zitvogel L, Madeo F, Kroemer G (2008) The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death. Cell Death Differ 15(9):1499–1509

    Article  Google Scholar 

  • Rossi A, Pakhomova ON, Pakhomov AG, Weygandt S, Bulysheva AA, Murray LE, Mollica PA, Muratori C (2019) Mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Sci Rep 9:431

    Article  Google Scholar 

  • Poznanski SM, Barra NG, Ashkar AA, Schertzer JD (2018) Immunometabolism of T cells and NK cells: metabolic control of effector and regulatory function. Inflamm Res 67(10):813–828

    Article  Google Scholar 

  • Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418(6894):191–195

    Article  Google Scholar 

  • Scheffer SR, Nave H, Korangy F, Schlote K, Pabst R, Jaffee EM, Manns MP, Greten TF (2003) Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo. Int J Cancer 103(2):205–211

    Article  Google Scholar 

  • Schoenbach KH, Beebe SJ, Buescher ES (2001) Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics 22(6):440–448

    Article  Google Scholar 

  • Schoenbach KH, Joshi RP, Kolb JF, Chen N, Stacey M, Buescher ES, Beebe SJ, Blackmon P (2004) Ultrashort electrical pulses open a new gateway into biological cells. Proc IEEE 92:1122–1137

    Article  Google Scholar 

  • Schoenbach KH, Joshi RP, Beebe SJ, Baum CE (2009) A Scaling Law for Membrane Permeabilization with Nanopulses. IEEE Trans Dielectrics Electr Insul 16:1224–1235

    Article  Google Scholar 

  • Schwartzberg PL, Sharpe AH, Speiser DE, Wherry EJ, Youngblood BA, Zehn D.Defining T cell exhaustion'.Nat Rev Immunol 19(11):665–674

    Google Scholar 

  • Smyth MJ, Crowe NY, Pellicci DG, Kyparissoudis K, Kelly JM, Takeda K, Yagita H, Godfrey DI. Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 99(4):1259–1266

    Google Scholar 

  • Sun J, Beilke J, Lanier L (2009) Adaptive immune features of natural killer cells. Nature 457:557–561

    Article  Google Scholar 

  • Sun JC, Lanier LL (2011) NK cell development, homeostasis, and function: parallels with CD8+ T cells. Nat Rev Immunol. 11(10):645–657

    Article  Google Scholar 

  • Sun JC, Ugolini S, Vivier E (2014) Immunological memory within the innate immune system. EMBO J 17:1295–1303

    Google Scholar 

  • Takayama H, LaRochelle WJ, Sharp R, Otsuka T, Kriebel P, Anver M, Aaronson SA, Merlino G (1997) Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc Natl Acad Sci U S A. 94(2):701–706

    Article  Google Scholar 

  • Tang H, Qiao J, Fu YX (2016) Immunotherapy and tumor microenvironment. Cancer Lett 370(1):85–90

    Article  Google Scholar 

  • Tao K, Fang M, Alroy J, Sahagian GG (2008) Imagable 4T1 model for the study of late stage breast cancer. BMC Cancer 8:228

    Article  Google Scholar 

  • Tesniere A, Apetoh L, Ghiringhelli F, Joza N, Panaretakis T, Kepp O, Schlemmer F, Zitvogel L, Kroemer G (2008a) Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol 20(5):504–511

    Article  Google Scholar 

  • Tesniere A, Panaretakis T, Kepp O, Apetoh L, Ghiringhelli F, Zitvogel L et al (2008b) Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 15:3–12

    Article  Google Scholar 

  • Trapani JA (1995) Target cell apoptosis induced by cytotoxic T cells and natural killer cells involves synergy between the pore-forming protein, perforin, and the serine protease, granzyme B. Aust N Z J Med 25(6):793–799

    Article  Google Scholar 

  • Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331(6013):44–49

    Article  Google Scholar 

  • Vucic D, Deshayes K, Ackerly H, Pisabarro MT, Kadkhodayan S, Fairbrother WJ, Dixit VM (2002) SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP). J Biol Chem 277(14):12275–12279

    Article  Google Scholar 

  • Williams MA, Bevan MJ (2007) Effector and memory CTL differentiation. Annu Rev Immunol 25:171–192

    Article  Google Scholar 

  • Wu RS, Kobie JJ, Besselsen DG, Fong TC, Mack VD, McEarchern JA, Akporiaye ET. Comparative analysis of IFN-gamma B7.1 and antisense TGF-beta gene transfer on the tumorigenicity of a poorly immunogenic metastatic mammary carcinoma. Cancer Immunol Immunother 50:229–240

    Google Scholar 

  • Yoneda T, Michigami T, Yi B, Williams PJ, Niewolna M, Hiraga T (2000) Actions of bisphosphonate on bone metastasis in animal models of breast carcinoma. Cancer 88(Suppl 12):2979–2988

    Google Scholar 

  • Yang H, Ma Y, Chen G, Zhou H, Yamazaki T, Klein C, Pietrocola F, Vacchelli E, Souquere S, Sauvat A, Zitvogel L, Kepp O, Kroemer G (2016) Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy. Oncoimmunology 5(6):e1149673

    Article  Google Scholar 

  • Zhang X, Zhang Y, Chen J, Wu Y, Zhang J, Wang J (2019) Nanosecond pulsed electric field inhibits malignant melanoma growth by inducing the change of systemic immunity. Med Oral Patol Oral Cir Bucal 24(4):e555–e561

    Google Scholar 

  • Zhu J, Paul WE (2008) CD4 T cells: fates, functions, and faults. Blood 112(5):1557–1569

    Google Scholar 

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  1. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA

    Stephen J. Beebe

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Beebe, S.J. (2021). usEPs as a Possible Immunotherapy. In: Ultrashort Electric Pulse Effects in Biology and Medicine. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-10-5113-5_19

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