Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Thermal Ablation Techniques
3. Immunomodulation Mediated by Ablation Techniques
3.1. Immune Changes Induced by RFA
3.2. Immune Changes Induced by MWA
3.3. Immune Changes Induced by Cryoablation
3.4. Immune Changes Induced by Other Ablation Techniques
4. Immunotherapy in HCC
5. Combination of Ablation Techniques with Immunotherapy in HCC
6. Discussion
Funding
Conflicts of Interest
Abbreviations
HCC | hepatocellular carcinoma |
RFA | radiofrequency ablation |
MWA | microwave ablation |
PD-1 | programmed cell death protein 1 |
PD-L1 | programmed death-ligand 1 |
HSP | heat shock proteins |
DCs | dendritic cells |
TAA | tumour-associated antigen |
CTLs | cytotoxic T lymphocytes |
IL | interleukin |
TGF | transforming growth factor |
IFN | interferon |
TNF | tumour necrosis factor |
NK | natural killer |
CTLA-4 | cytotoxic T-lymphocyte associated protein 4 |
TIM-3 | T cell immunoglobulin and mucin-domain containing 3 |
LAG-3 | lymphocyte activation gene 3 |
TIGIT | T cell immunoreceptor with Ig and ITIM domains |
VISTA | V-domain Ig Suppressor of T cell Activation |
VEGF | vascular endothelial growth factor |
PBMCs | peripheral blood mononuclear cells |
References
- Macek Jilkova, Z.; Aspord, C.; Decaens, T. Predictive Factors for Response to PD-1/PD-L1 Checkpoint Inhibition in the Field of Hepatocellular Carcinoma: Current Status and Challenges. Cancers 2019, 11, 1554. [Google Scholar] [CrossRef] [Green Version]
- Pinato, D.J.; Guerra, N.; Fessas, P.; Murphy, R.; Mineo, T.; Mauri, F.A.; Mukherjee, S.K.; Thursz, M.; Wong, C.N.; Sharma, R.; et al. Immune-based therapies for hepatocellular carcinoma. Oncogene 2020, 39, 3620–3637. [Google Scholar] [CrossRef] [Green Version]
- Nault, J.C.; Sutter, O.; Nahon, P.; Ganne-Carrié, N.; Séror, O. Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. J. Hepatol. 2018, 68, 783–797. [Google Scholar] [CrossRef] [Green Version]
- Poulou, L.S.; Botsa, E.; Thanou, I.; Ziakas, P.D.; Thanos, L. Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World J. Hepatol. 2015, 7, 1054–1063. [Google Scholar] [CrossRef] [PubMed]
- Chu, K.F.; Dupuy, D.E. Thermal ablation of tumours: Biological mechanisms and advances in therapy. Nat. Rev. Cancer 2014, 14, 199–208. [Google Scholar] [CrossRef] [PubMed]
- McGahan, J.P.; Browning, P.D.; Brock, J.M.; Tesluk, H. Hepatic ablation using radiofrequency electrocautery. Investig. Radiol. 1990, 25, 267–270. [Google Scholar] [CrossRef] [PubMed]
- Glassberg, M.B.; Ghosh, S.; Clymer, J.W.; Qadeer, R.A.; Ferko, N.C.; Sadeghirad, B.; Wright, G.W.; Amaral, J.F. Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: A systematic review and meta-analysis. OncoTargets Ther. 2019, 12, 6407–6438. [Google Scholar] [CrossRef] [Green Version]
- Seki, T.; Wakabayashi, M.; Nakagawa, T.; Itho, T.; Shiro, T.; Kunieda, K.; Sato, M.; Uchiyama, S.; Inoue, K. Ultrasonically guided percutaneous microwave coagulation therapy for small hepatocellular carcinoma. Cancer 1994, 74, 817–825. [Google Scholar] [CrossRef]
- Mehta, A.; Oklu, R.; Sheth, R.A. Thermal Ablative Therapies and Immune Checkpoint Modulation: Can Locoregional Approaches Effect a Systemic Response? Gastroenterol. Res. Pract. 2016, 2016. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Wang, W.; Pan, H.; Ma, G.; Shi, X.; Xie, H.; Liu, X.; Ding, Q.; Zhou, W.; Wang, S. Microwave ablation combined with OK-432 induces Th1-type response and specific antitumor immunity in a murine model of breast cancer. J. Transl. Med. 2017, 15, 23. [Google Scholar] [CrossRef] [Green Version]
- Huang, K.W.; Jayant, K.; Lee, P.H.; Yang, P.C.; Hsiao, C.Y.; Habib, N.; Sodergren, M.H. Positive Immuno-Modulation Following Radiofrequency Assisted Liver Resection in Hepatocellular Carcinoma. J. Clin. Med. 2019, 8, 385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ng, J.; Dai, T. Radiation therapy and the abscopal effect: A concept comes of age. Ann. Transl. Med. 2016, 4, 118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haen, S.P.; Gouttefangeas, C.; Schmidt, D.; Boss, A.; Clasen, S.; von Herbay, A.; Kosan, B.; Aebert, H.; Pereira, P.L.; Rammensee, H.G. Elevated serum levels of heat shock protein 70 can be detected after radiofrequency ablation. Cell Stress Chaperones 2011, 16, 495–504. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dromi, S.A.; Walsh, M.P.; Herby, S.; Traughber, B.; Xie, J.; Sharma, K.V.; Sekhar, K.P.; Luk, A.; Liewehr, D.J.; Dreher, M.R.; et al. Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology 2009, 251, 58–66. [Google Scholar] [CrossRef] [Green Version]
- 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, 1448–1457. [Google Scholar] [CrossRef] [Green Version]
- Rochigneux, P.; Nault, J.C.; Mallet, F.; Chretien, A.S.; Barget, N.; Garcia, A.J.; Del Pozo, L.; Bourcier, V.; Blaise, L.; Grando-Lemaire, V.; et al. Dynamic of systemic immunity and its impact on tumor recurrence after radiofrequency ablation of hepatocellular carcinoma. Oncoimmunology 2019, 8. [Google Scholar] [CrossRef] [Green Version]
- Nobuoka, D.; Motomura, Y.; Shirakawa, H.; Yoshikawa, T.; Kuronuma, T.; Takahashi, M.; Nakachi, K.; Ishii, H.; Furuse, J.; Gotohda, N.; et al. Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes. Int. J. Oncol. 2012, 40, 63–70. [Google Scholar]
- Tu, J.F.; Ding, Y.H.; Ying, X.H.; Wu, F.Z.; Zhou, X.M.; Zhang, D.K.; Zou, H.; Ji, J.S. Regulatory T cells, especially ICOS(+) FOXP3(+) regulatory T cells, are increased in the hepatocellular carcinoma microenvironment and predict reduced survival. Sci. Rep. 2016, 6, 35056. [Google Scholar] [CrossRef]
- Ahmad, F.; Gravante, G.; Bhardwaj, N.; Strickland, A.; Basit, R.; West, K.; Sorge, R.; Dennison, A.R.; Lloyd, D.M. Changes in interleukin-1beta and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections. Am. J. Surg. 2010, 200, 500–506. [Google Scholar] [CrossRef]
- Ahmad, F.; Gravante, G.; Bhardwaj, N.; Strickland, A.; Basit, R.; West, K.; Sorge, R.; Dennison, A.R.; Lloyd, D.M. Renal effects of microwave ablation compared with radiofrequency, cryotherapy and surgical resection at different volumes of the liver treated. Liver Int. Off. J. Int. Assoc. Stud. Liver 2010, 30, 1305–1314. [Google Scholar] [CrossRef]
- Dong, B.W.; Zhang, J.; Liang, P.; Yu, X.L.; Su, L.; Yu, D.J.; Ji, X.L.; Yu, G. Sequential pathological and immunologic analysis of percutaneous microwave coagulation therapy of hepatocellular carcinoma. Int. J. Hyperth. Off. J. Eur. Soc. Hyperth. Oncol. North 2003, 19, 119–133. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Hou, X.; Cai, H.; Zhuang, X. Effects of microwave ablation on T-cell subsets and cytokines of patients with hepatocellular carcinoma. Minim. Invasive Ther. Allied Technol. MITAT Off. J. Soc. Minim. Invasive Ther. 2017, 26, 207–211. [Google Scholar] [CrossRef] [PubMed]
- Slovak, R.; Ludwig, J.M.; Gettinger, S.N.; Herbst, R.S.; Kim, H.S. Immuno-thermal ablations—boosting the anticancer immune response. J. Immunother. Cancer 2017, 5, 78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aarts, B.M.; Klompenhouwer, E.G.; Rice, S.L.; Imani, F.; Baetens, T.; Bex, A.; Horenblas, S.; Kok, M.; Haanen, J.B.A.G.; Beets-Tan, R.G.H.; et al. Cryoablation and immunotherapy: An overview of evidence on its synergy. Insights Imaging 2019, 10, 53. [Google Scholar] [CrossRef]
- Abdo, J.; Cornell, D.L.; Mittal, S.K.; Agrawal, D.K. Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers. Front. Oncol. 2018, 8, 85. [Google Scholar] [CrossRef]
- Erinjeri, J.P.; Thomas, C.T.; Samoilia, A.; Fleisher, M.; Gonen, M.; Sofocleous, C.T.; Thornton, R.H.; Siegelbaum, R.H.; Covey, A.M.; Brody, L.A.; et al. Image-guided thermal ablation of tumors increases the plasma level of interleukin-6 and interleukin-10. J. Vasc. Interv. Radiol. JVIR 2013, 24, 1105–1112. [Google Scholar] [CrossRef] [Green Version]
- Osada, S.; Imai, H.; Tomita, H.; Tokuyama, Y.; Okumura, N.; Matsuhashi, N.; Sakashita, F.; Nonaka, K. Serum cytokine levels in response to hepatic cryoablation. J. Surg. Oncol. 2007, 95, 491–498. [Google Scholar] [CrossRef]
- Zhou, L.; Fu, J.L.; Lu, Y.Y.; Fu, B.Y.; Wang, C.P.; An, L.J.; Wang, X.Z.; Zeng, Z.; Zhou, C.B.; Yang, Y.P.; et al. cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma. J. Gastroenterol. 2010, 45, 968–978. [Google Scholar] [CrossRef]
- White, S.B.; Zhang, Z.; Chen, J.; Gogineni, V.R.; Larson, A.C. Early Immunologic Response of Irreversible Electroporation versus Cryoablation in a Rodent Model of Pancreatic Cancer. J. Vasc. Interv. Radiol. JVIR 2018, 29, 1764–1769. [Google Scholar] [CrossRef]
- Vivas, I.; Iribarren, K.; Lozano, T.; Cano, D.; Lasarte-Cia, A.; Chocarro, S.; Gorraiz, M.; Sarobe, P.; Hervás-Stubbs, S.; Bilbao, J.I.; et al. Therapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma. J. Vasc. Interv. Radiol. JVIR 2019, 30, 1098–1105. [Google Scholar] [CrossRef]
- Johnston, M.P.; Khakoo, S.I. Immunotherapy for hepatocellular carcinoma: Current and future. World J. Gastroenterol. WJG 2019, 25, 2977–2989. [Google Scholar] [CrossRef] [PubMed]
- Wei, S.C.; Duffy, C.R.; Allison, J.P. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov. 2018, 8, 1069–1086. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Macek Jilkova, Z.; Aspord, C.; Kurma, K.; Granon, A.; Sengel, C.; Sturm, N.; Marche, P.N.; Decaens, T. Immunologic Features of Patients With Advanced Hepatocellular Carcinoma Before and During Sorafenib or Anti-programmed Death-1/Programmed Death-L1 Treatment. Clin. Transl. Gastroenterol. 2019. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kudo, M. Scientific Rationale for Combined Immunotherapy with PD-1/PD-L1 Antibodies and VEGF Inhibitors in Advanced Hepatocellular Carcinoma. Cancers 2020, 12, 1089. [Google Scholar] [CrossRef]
- Finn, R.S.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.Y.; Kudo, M.; Breder, V.; Merle, P.; Kaseb, A.O.; et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020, 382, 1894–1905. [Google Scholar] [CrossRef]
- Greten, T.F.; Mauda-Havakuk, M.; Heinrich, B.; Korangy, F.; Wood, B.J. Combined locoregional-immunotherapy for liver cancer. J. Hepatol. 2019, 70, 999–1007. [Google Scholar] [CrossRef] [Green Version]
- Cui, J.; Wang, N.; Zhao, H.; Jin, H.; Wang, G.; Niu, C.; Terunuma, H.; He, H.; Li, W. Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma. Int. J. Cancer 2014, 134, 342–351. [Google Scholar] [CrossRef]
- Zhou, P.; Liang, P.; Dong, B.; Yu, X.; Han, Z.; Xu, Y. Phase clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma. Cancer Biol. Ther. 2011, 11, 450–456. [Google Scholar] [CrossRef] [Green Version]
- Niu, L.Z.; Li, J.L.; Zeng, J.Y.; Mu, F.; Liao, M.T.; Yao, F.; Li, L.; Liu, C.Y.; Chen, J.B.; Zuo, J.S.; et al. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer. World J. Gastroenterol. WJG 2013, 19, 3473–3480. [Google Scholar] [CrossRef]
- Duffy, A.G.; Ulahannan, S.V.; Makorova-Rusher, O.; Rahma, O.; Wedemeyer, H.; Pratt, D.; Davis, J.L.; Hughes, M.S.; Heller, T.; ElGindi, M.; et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J. Hepatol. 2017, 66, 545–551. [Google Scholar] [CrossRef] [Green Version]
- Shi, L.; Wang, J.; Ding, N.; Zhang, Y.; Zhu, Y.; Dong, S.; Wang, X.; Peng, C.; Zhou, C.; Zhou, L.; et al. Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy. Nat. Commun. 2019, 10, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Macek Jilkova, Z.; Kurma, K.; Decaens, T. Animal Models of Hepatocellular Carcinoma: The Role of Immune System and Tumor Microenvironment. Cancers 2019, 11, 1487. [Google Scholar] [CrossRef] [PubMed] [Green Version]
First Author Name et al. | Year | Ablation Technique | Number of Subjects (n) | Immunomodulation Observed |
---|---|---|---|---|
Haen et al. [13] | 2011 | RFA | 4 | Increase in serum levels of HSP-70 |
Nobuoka et al. [17] | 2012 | RFA | 9 | Increase in circulating glypican-3-specific cytotoxic T cells |
Mizukoshi et al. [15] | 2013 | RFA | 69 | Increase in the number of circulating TAA-specific T cells, mainly the central memory phenotype (CD45RA-/CCR7+) |
Huang et al. [11] | 2019 | RFA | 6 | Decrease in circulating regulatory T cells; Increase in circulating CD8+ T cells and CD4+/CD45RO+ memory T cells; Decrease in TGF-β, IL-10; Increase in IFN-γ |
Rochigneux et al. [16] | 2019 | RFA | 80 | Modifications of NKp30+ NK cells and plasmacytoid DC |
Dong et al. [21] | 2003 | MWA | 82 | Increase in tumour-infiltrating NK cells, macrophages and T cells |
Zhang et al. [22] | 2017 | MWA | 45 | Increase in circulating CD3+ cells and CD4+ cells; Increase in IL-12; Decrease in IL-4 and IL-10 |
Zhou et al. [28] | 2010 | Cryoablation | 111 | Association of circulating regulatory T cells with tumour regression or progression Decrease in CD8+, CD4+, and FoxP3+ cells around the cryoablation zones. |
Clinical Trials (Identifier) | Phase | Intervention/Treatment | Number of Participants | Estimated Study Completion Date |
---|---|---|---|---|
LKSM001 (NCT03674073) | Phase 1 | Personalized neoantigen-based DC vaccine in combination with MWA | 24 | December 2020 |
RI11330 (NCT03864211) | Phase 1/2 | Thermal ablation, RFA or MWA, followed by Toripalimab | 120 | March 2021 |
ZS-IR-2019B (NCT04220944) | Phase 1 | MWA in combination with simultaneous TACE plus Sintilimab | 45 | September 2021 |
160135 (NCT02821754) | Phase 2 | Combination of tremelimumab and durvalumab with ablative therapies, TACE, RFA or cryoablation | 90 | December 2021 |
HCC 004 (NCT02678013) | Phase 3 | RFA combined with highly-purified CTLs | 210 | January 2022 |
IMMULAB (NCT03753659) | Phase 2 | Pembrolizumab in combination with local ablation via RFA or MWA | 30 | September 2022 |
EMERALD-2 (NCT03847428) | Phase 3 | Durvalumab in combination with bevacizumab or durvalumab alone in patients with hepatocellular carcinoma who are at high risk of recurrence after surgical resection or ablation | 888 | June 2023 |
S2019-128-02 (NCT04204577) | Phase 2 | Thermal ablation combined with Apatinib and Carilimub | 90 | November 2023 |
MK-3475-937/KEYNOTE-937 (NCT03867084) | Phase 3 | Pembrolizumab in comparison with placebo in HCC patients with complete radiological response after surgical resection or ablation | 950 | June 2025 |
CheckMate 9DX (NCT03383458) | Phase 3 | Nivolumab in comparison with placebo in HCC patients at high risk of recurrence after surgical resection or ablation | 530 | June 2025 |
1102320191018 (NCT04150744) | Phase 2 | RFA combined with Carrizumab and Apatinib | 120 | December 2026 |
IMbrave050 (NCT04102098) | Phase 3 | Atezolizumab plus bevacizumab in comparison with active surveillance in HCC patients at high risk of recurrence after surgical resection or ablation | 662 | July 2027 |
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Dumolard, L.; Ghelfi, J.; Roth, G.; Decaens, T.; Macek Jilkova, Z. Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2020, 21, 4398. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124398
Dumolard L, Ghelfi J, Roth G, Decaens T, Macek Jilkova Z. Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2020; 21(12):4398. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124398
Chicago/Turabian StyleDumolard, Lucile, Julien Ghelfi, Gael Roth, Thomas Decaens, and Zuzana Macek Jilkova. 2020. "Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma" International Journal of Molecular Sciences 21, no. 12: 4398. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124398