Immune Response to Locoregional Therapy

Abstract

The immune response to cancer is an ongoing area of interest and is the focus of newer systemic agents. Liver-directed therapy has been the standard treatment for primary and metastatic disease limited to the liver. It is increasingly being recognized that these therapies may influence a broader systemic response and immune activation. The clinical and translational data supporting this phenomenon are reviewed herein. The findings and potential impact of the immune response to liver-directed therapies are summarized in this article.

Keywords

liver-directed therapy - immune system - inflammatory response

Publication History

Received: 27 September 2021

Accepted: 24 November 2021

Article published online:
04 January 2022

• References

• 1 Lu C, Rong D, Zhang B. et al. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities. Mol Cancer 2019; 18 (01) 130
• 2 Borst J, Ahrends T, Bąbała N, Melief CJM, Kastenmüller W. CD4⁺ T cell help in cancer immunology and immunotherapy. Nat Rev Immunol 2018; 18 (10) 635-647
• 3 Mizukoshi E, Yamashita T, Arai K. et al. Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma. Hepatology 2013; 57 (04) 1448-1457
• 4 Liao Y, Wang B, Huang ZL. et al. Increased circulating Th17 cells after transarterial chemoembolization correlate with improved survival in stage III hepatocellular carcinoma: a prospective study. PLoS One 2013; 8 (04) e60444
• 5 Ayaru L, Pereira SP, Alisa A. et al. Unmasking of α-fetoprotein-specific CD4(+) T cell responses in hepatocellular carcinoma patients undergoing embolization. J Immunol 2007; 178 (03) 1914-1922
• 6 Kohles N, Nagel D, Jüngst D, Stieber P, Holdenrieder S. Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in liver cancer patients receiving transarterial chemoembolization therapy. Tumour Biol 2012; 33 (06) 2401-2409
• 7 Kim MJ, Jang JW, Oh BS. et al. Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma. Cytokine 2013; 64 (02) 516-522
• 8 Fan W, Zhang Y, Wang Y, Yao X, Yang J, Li J. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization. PLoS One 2015; 10 (03) e0119312
• 9 Huang ZL, Luo J, Chen MS, Li JQ, Shi M. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization. J Vasc Interv Radiol 2011; 22 (05) 702-709
• 10 Sullivan KM, Groeschl RT, Turaga KK. et al. Neutrophil-to-lymphocyte ratio as a predictor of outcomes for patients with hepatocellular carcinoma: a Western perspective. J Surg Oncol 2014; 109 (02) 95-97
• 11 Tischfield D, Gurevich A, Johnson O. et al. Transarterial embolization modulates the immune response within target and non-target hepatocellular carcinomas. bioRxiv 2020; :2020.11.07.372896
• 12 Avritscher R, Jo N, Polak U. et al. Hepatic arterial bland embolization increases Th17 cell infiltration in a syngeneic rat model of hepatocellular carcinoma. Cardiovasc Intervent Radiol 2020; 43 (02) 311-321
• 13 Gómez V, Mustapha R, Ng K, Ng T. Radiation therapy and the innate immune response: clinical implications for immunotherapy approaches. Br J Clin Pharmacol 2020; 86 (09) 1726-1735
• 14 Mole RH. Whole body irradiation; radiobiology or medicine?. Br J Radiol 1953; 26 (305) 234-241
• 15 Chew V, Lee YH, Pan L. et al. Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma. Gut 2019; 68 (02) 335-346
• 16 Craciun L, de Wind R, Demetter P. et al. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer 2020; 20 (01) 135
• 17 Carr BI. Hepatic arterial ⁹⁰yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 2004; 10 (2, Suppl 1): S107-S110
• 18 Salem R, Lewandowski RJ, Atassi B. et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16 (12) 1627-1639
• 19 Domouchtsidou A, Barsegian V, Mueller SP. et al. Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy. Cancer Immunol Immunother 2018; 67 (05) 843-853
• 20 D'Emic N, Engelman A, Molitoris J. et al. Prognostic significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients treated with selective internal radiation therapy. J Gastrointest Oncol 2016; 7 (02) 269-277
• 21 Zerbini A, Pilli M, Laccabue D. et al. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology 2010; 138 (05) 1931-1942
• 22 Hänsler J, Wissniowski TT, Schuppan D. et al. Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases. World J Gastroenterol 2006; 12 (23) 3716-3721
• 23 Erinjeri JP, Thomas CT, Samoilia A. et al. Image-guided thermal ablation of tumors increases the plasma level of interleukin-6 and interleukin-10. J Vasc Interv Radiol 2013; 24 (08) 1105-1112
• 24 Zerbini A, Pilli M, Fagnoni F. et al. Increased immunostimulatory activity conferred to antigen-presenting cells by exposure to antigen extract from hepatocellular carcinoma after radiofrequency thermal ablation. J Immunother 2008; 31 (03) 271-282
• 25 Wisnowski TT, Hänsler J, Neureiter D. et al. Erratum: activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits (cancer research (October 1, 2003) (6496–6500)). Cancer Res 2003; 63 (21) 7543
• 26 Dromi SA, Walsh MP, Herby S. et al. Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology 2009; 251 (01) 58-66
• 27 Jansen MC, van Hillegersberg R, Schoots IG. et al. Cryoablation induces greater inflammatory and coagulative responses than radiofrequency ablation or laser induced thermotherapy in a rat liver model. Surgery 2010; 147 (05) 686-695
• 28 Zhang Z, Li W, Procissi D, Tyler P, Omary RA, Larson AC. Rapid dramatic alterations to the tumor microstructure in pancreatic cancer following irreversible electroporation ablation. Nanomedicine (Lond) 2014; 9 (08) 1181-1192
• 29 White SB, Zhang Z, Chen J, Gogineni VR, Larson AC. Early immunologic response of irreversible electroporation versus cryoablation in a rodent model of pancreatic cancer. J Vasc Interv Radiol 2018; 29 (12) 1764-1769
• 30 Yang J, Eresen A, Shangguan J, Ma Q, Yaghmai V, Zhang Z. Irreversible electroporation ablation overcomes tumor-associated immunosuppression to improve the efficacy of DC vaccination in a mice model of pancreatic cancer. OncoImmunology 2021; 10 (01) 1875638