Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report

Yi,Yongxiang; Han,Jianbo; Fang,Yuan; Liu,Dongxiao; Wu,Zuoyou; Wang,Lili; Zhao,Liang; Wei,Qiang

doi:10.3892/mco.2016.925

Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report

Authors:
- Yongxiang Yi
- Jianbo Han
- Yuan Fang
- Dongxiao Liu
- Zuoyou Wu
- Lili Wang
- Liang Zhao
- Qiang Wei
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Affiliations: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210003, P.R. China, Department of Pathology, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210003, P.R. China, Biological Treatment Center, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210003, P.R. China, Department of Ultrasonography, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210003, P.R. China
Published online on: June 10, 2016 https://doi.org/10.3892/mco.2016.925
Pages: 337-341

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Abstract

Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles‑pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)‑γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T‑cell response to SMMC‑7721‑derived DRibbles vaccine. The α‑fetoprotein level decreased from 103,295 to 5 ng̸ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post‑combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post‑combination therapy. The ELISPOT data revealed a low antigen‑specific T‑cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen‑specific T‑cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN‑γ was produced by CD4+ T cells, whereas a low CD8+ T‑cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen‑specific T‑cell response aimed to treat recurrent HCC may be induced through stimulation by the DC‑DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC‑DRibbles vaccine as a therapeutic strategy for patients with HCC recurrence following hepatectomy.

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1	Au JS and Frenette CT: Management of hepatocellular carcinoma: Current status and future directions. Gut Liver. 9:437–448. 2015. View Article : Google Scholar : PubMed/NCBI
2	Colagrande S, Regini F, Taliani GG, Nardi C and Inghilesi AL: Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up. World J Hepatol. 7:1041–1053. 2015. View Article : Google Scholar : PubMed/NCBI
3	Takeishi K, Maeda T, Tsujita E, Yamashita Y, Harada N, Itoh S, Harimoto N, Ikegami T, Yoshizumi T, Shirabe K and Maehara Y: Predictors of intrahepatic multiple recurrences after curative hepatectomy for hepatocellular carcinoma. Anticancer Res. 35:3061–3066. 2015.PubMed/NCBI
4	Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI
5	Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009. View Article : Google Scholar : PubMed/NCBI
6	Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N and Geschwind JF: Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol. 29:3960–3967. 2011. View Article : Google Scholar : PubMed/NCBI
7	Han G, Yang J, Shao G, Teng G, Wang M, Yang J, Liu Z, Feng G, Yang R, Lu L, et al: Sorafenib in combination with transarterial chemoembolization in Chinese patients with hepatocellular carcinoma: A subgroup interim analysis of the START trial. Future Oncol. 9:403–410. 2013. View Article : Google Scholar : PubMed/NCBI
8	Bhoori S, Toffanin S, Sposito C, Germini A, Pellegrinelli A, Lampis A and Mazzaferro V: Personalized molecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: A proof of principle. J Hepatol. 52:771–775. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yi Y, Zhou Z, Shu S, Fang Y, Twitty C, Hilton TL, Aung S, Urba WJ, Fox BA, Hu HM and Li Y: Autophagy-assisted antigen cross-presentation: Autophagosome as the argo of shared tumor-specific antigens and DAMPs. Oncoimmunology. 1:976–978. 2012. View Article : Google Scholar : PubMed/NCBI
10	Ye W, Xing Y, Paustian C, van de Ven R, Moudgil T, Hilton TL, Fox BA, Urba WJ, Zhao W and Hu HM: Cross-presentation of viral antigens in dribbles leads to efficient activation of virus-specific human memory T cells. J Transl Med. 12:1002014. View Article : Google Scholar : PubMed/NCBI
11	Su S, Zhou H, Xue M, Liu JY, Ding L, Cao M, Zhou ZX, Hu HM and Wang LX: Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models. Asian Pac J Cancer Prev. 14:3109–3116. 2013. View Article : Google Scholar : PubMed/NCBI
12	Bruix J and Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology. 42:1208–1236. 2005. View Article : Google Scholar : PubMed/NCBI
13	Lapenta C, Santini SM, Spada M, Donati S, Urbani F, Accapezzato D, Franceschini D, Andreotti M, Barnaba V and Belardelli F: IFN-alpha-conditioned dendritic cells are highly efficient in inducing cross-priming CD8⁺ T cells against exogenous viral antigens. Eur J Immunol. 36:2046–2060. 2006. View Article : Google Scholar : PubMed/NCBI
14	Li Y, Wang LX, Pang P, Cui Z, Aung S, Haley D, Fox BA, Urba WJ and Hu HM: Tumor-derived autophagosome vaccine: Mechanism of cross-presentation and therapeutic efficacy. Clin Cancer Res. 17:7047–7057. 2011. View Article : Google Scholar : PubMed/NCBI
15	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D and Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
16	Choi AM, Ryter SW and Levine B: Autophagy in human health and disease. N Engl J Med. 368:1845–1846. 2013. View Article : Google Scholar : PubMed/NCBI
17	Li Y, Wang LX, Yang G, Hao F, Urba WJ and Hu HM: Efficient cross-presentation depends on autophagy in tumor cells. Cancer Res. 68:6889–6895. 2008. View Article : Google Scholar : PubMed/NCBI
18	Li Y, Hahn T, Garrison K, Cui ZH, Thorburn A, Thorburn J, Hu HM and Akporiaye ET: The vitamin E analogue α-TEA stimulates tumor autophagy and enhances antigen cross-presentation. Cancer Res. 72:3535–3545. 2012. View Article : Google Scholar : PubMed/NCBI
19	Twitty CG, Jensen SM, Hu HM and Fox BA: Tumor-derived autophagosome vaccine: Induction of cross-protective immune responses against short-lived proteins through a p62-dependent mechanism. Clin Cancer Res. 17:6467–6481. 2011. View Article : Google Scholar : PubMed/NCBI
20	Segura E and Amigorena S: Cross-presentation by human dendritic cell subsets. Immunol Lett. 158:73–78. 2014. View Article : Google Scholar : PubMed/NCBI
21	Boltjes A and van Wijk F: Human dendritic cell functional specialization in steady-state and inflammation. Front Immunol. 5:1312014. View Article : Google Scholar : PubMed/NCBI
22	Schreibelt G, Klinkenberg LJ, Cruz LJ, Tacken PJ, Tel J, Kreutz M, Adema GJ, Brown GD, Figdor CG and de Vries IJ: The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3⁺ myeloid dendritic cells. Blood. 119:2284–2292. 2012. View Article : Google Scholar : PubMed/NCBI
23	Poulin LF, Salio M, Griessinger E, Anjos-Afonso F, Craciun L, Chen JL, Keller AM, Joffre O, Zelenay S, Nye E, et al: Characterization of human DNGR-1⁺ BDCA3⁺ leukocytes as putative equivalents of mouse CD8alpha⁺ dendritic cells. J Exp Med. 207:1261–1271. 2010. View Article : Google Scholar : PubMed/NCBI
24	Ng D and Gommerman JL: The Regulation of Immune Responses by DC Derived Type I IFN. Front Immunol. 4:942013. View Article : Google Scholar : PubMed/NCBI