Multiple courses of immunotherapy with different immune cell types for patients with hepatocellular carcinoma after microwave ablation

Yu,Ming‑An; Liang,Ping; Yu,Xiao‑Ling; Han,Zhi‑Yu; Dong,Xue‑Juan; Wang,Yu; Cheng,Chao; Li,Xin

doi:10.3892/etm.2015.2681

Multiple courses of immunotherapy with different immune cell types for patients with hepatocellular carcinoma after microwave ablation

Authors:
- Ming‑An Yu
- Ping Liang
- Xiao‑Ling Yu
- Zhi‑Yu Han
- Xue‑Juan Dong
- Yu Wang
- Chao Cheng
- Xin Li
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Affiliations: Interventional Ultrasound Center, China‑Japan Friendship Hospital, Beijing 100029, P.R. China, Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Research and Development, Beijing Yongtai Immune Application Technology Co., Ltd., Beijing 101111, P.R. China
Published online on: August 14, 2015 https://doi.org/10.3892/etm.2015.2681
Pages: 1460-1466

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Abstract

The aim of the present study was to investigate the therapeutic efficacy of immunotherapy after microwave ablation (MWA), which was used to improve liver function, reduce the recurrence rate and enhance survival period in patients with hepatocellular carcinoma (HCC). Between February 2009 and December 2010, 14 patients received immunotherapy after MWA (immunotherapy group) and 15 patients received MWA alone with no post‑ablated adjuvant therapy (control group). Immune and liver parameters, recurrence rate and survival time were recorded. The absolute lymphocyte count in the immunotherapy group exceeded that in the control group after 3 courses of immunotherapy (P<0.05). No significant differences were detected in the lymphocyte subset distribution in the control and immunotherapy patients prior to ablation (P>0.05); however, certain cytotoxic subsets (CD3+/CD8+, CD8+CD28+ and CD3+CD16+CD56+ T cells) were over‑represented and negative regulatory or helper subsets (CD4+CD8+, CD4+, CD4+CD25+) were under‑represented in the immunotherapy group between 1 and 12 months after immunotherapy (P<0.05). After 2 courses of immunotherapy the proliferation rate of myeloid dendritic cells and T lymphocytes, including CD3+/CD8+ lymphocytes, significantly increased (P<0.05 and P<0.01, respectively). In addition, the level of albumin in the immunotherapy group exceeded that in the control group after 3 courses of immunotherapy (P<0.05). However, the rate of disease‑free survival and overall survival within 16 months of MWA did not differ significantly between the two groups (P>0.05). In conclusion, the results of the present study indicate that immunotherapy improves the immune status and liver function of patients with HCC.

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1	El Serag HB: Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127 (5 Suppl 1). 27–34. 2004.
2	Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E and La Vecchia C: Trends in mortality from hepatocellular carcinoma in Europe, 1980–2004. Hepatology. 48:137–145. 2008. View Article : Google Scholar : PubMed/NCBI
3	Kaibori M, Ishizaki M, Matsui K and Kwon AH: Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol. 102:462–468. 2010. View Article : Google Scholar : PubMed/NCBI
4	Funaki NO, Tanaka J, Seto SI, Kasamatsu T, Kaido T and Imamura M: Hematogenous spreading of hepatocellular carcinoma cells: Possible participation in recurrence in the liver. Hepatology. 25:564–568. 1997. View Article : Google Scholar : PubMed/NCBI
5	Bruix J, Sherman M, Llovet JM, et al: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European association for the study of the liver. J Hepatol. 35:421–430. 2001. View Article : Google Scholar : PubMed/NCBI
6	Takayama T, Sekine T, Makuuchi M, et al: Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: A randomised trial. Lancet. 356:802–807. 2000. View Article : Google Scholar : PubMed/NCBI
7	Hui D, Qiang L, Jian W, Ti Z and Da-Lu K: A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma. Dig Liver Dis. 41:36–41. 2009. View Article : Google Scholar : PubMed/NCBI
8	Weng DS, Zhou J, Zhou QM, et al: Minimally invasive treatment combined with cytokine-induced killer cells therapy lower the short-term recurrence rates of hepatocellular carcinomas. J Immunother. 31:63–71. 2008. View Article : Google Scholar : PubMed/NCBI
9	Zhou WP, Wu MC and Chen H: The effects of combined hepatectomy and immuno-chemotherapy on postoperative recurrence rate of primary liver cancer. Zhong Hua Wai Ke Za Zhi. 33:35–37. 1995.(In Chinese).
10	Zhong JH, Ma L, Wu LC, et al: Adoptive immunotherapy for postoperative hepatocellular carcinoma: A systematic review. Int J Clin Pract. 66:21–27. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ma H, Zhang Y, Wang Q, et al: Therapeutic safety and effects of adjuvant autologous RetroNectin activated killer cell immunotherapy for patients with primary hepatocellular carcinoma after radiofrequency ablation. Cancer Biol Ther. 9:903–907. 2010. View Article : Google Scholar : PubMed/NCBI
12	Zhou P, Liang P, Dong B, Yu X, Han Z and Xu Y: Phase clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma. Cancer Biol Ther. 11:450–456. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhang J, Ye L, Zhang J, Lin M, He S, Mao X, Zhou X and Zhi F: MELD scores and Child-Pugh classifications predict the outcomes of ERCP in cirrhotic patients with choledocholithiasis: A retrospective cohort study. Medicine (Baltimore). 94:e4332015. View Article : Google Scholar : PubMed/NCBI
14	Liu SR, Liang P, Yu XL, Cheng ZG, Han ZY and Yu J: Percutaneous microwave ablation for liver tumours adjacent to the marginal angle. Int J Hyperthermia. 30:306–311. 2014. View Article : Google Scholar : PubMed/NCBI
15	Usuda S, Yoshizawa K, Yabu K and Kiyosawa K: Immunological responses against an autologous human hepatocellular carcinoma cell line. J Gastroenterol Hepatol. 8:517–523. 1993. View Article : Google Scholar : PubMed/NCBI
16	Kong L, Yao SK, Liu JX and Wang N: The prognostic value of cellular immunity function in patients with hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 13:194–197. 2005.PubMed/NCBI
17	Deguchi Y, Yoshimatsu K and Endo S: Natural killer-like T cell lymphoma of the small intestine: Report of a case. Surg Today. 36:474–477. 2006. View Article : Google Scholar : PubMed/NCBI
18	Liu HR and Li WM: Treg-specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma. IUBMB Life. 67:355–360. 2015. View Article : Google Scholar : PubMed/NCBI
19	Passalacqua G, BaenaCagnani CE, Bousquet J, Canonica GW, Casale TB, Cox L, Durham SR, LarenasLinnemann D, Ledford D, Pawankar R, et al: Grading local side effects of sublingual immunotherapy for respiratory allergy: Speaking the same language. J Allergy Clin Immunol. 132:93–98. 2013. View Article : Google Scholar : PubMed/NCBI
20	Cox L, LarenasLinnemann D, Lockey RF and Passalacqua G: Speaking the same language: The World Allergy Organization subcutaneous immunotherapy systemic reaction grading system. J Allergy Clin Immunol. 25:569–574. 2010. View Article : Google Scholar
21	Song R, Ikeguchi M, Zhou G and Kuo MT: Identification and characterization of a hepatoma cell-specific enhancer in the mouse multidrug resistance mdr1b promoter. J Biol Chem. 270:25468–25474. 1995. View Article : Google Scholar : PubMed/NCBI
22	Chen TM, Lin CC, Huang PT and Wen CF: Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation. J Gastroenterol Hepatol. 27:553–561. 2012. View Article : Google Scholar : PubMed/NCBI
23	Koh YW, Kang HJ, Park C, et al: The ratio of the absolute lymphocyte count to the absolute monocyte count is associated with prognosis in Hodgkin's lymphoma: correlation with tumor-associated macrophages. Oncologist. 17:871–880. 2012. View Article : Google Scholar : PubMed/NCBI
24	Lee CS: Lymphocytes and their subsets in the peripheral blood of hepatocellular carcinoma patients. J Formos Med Assoc. 90:626–630. 1991.PubMed/NCBI
25	Wang JX, Liu GH, Fan YZ, et al: Effects of cytotoxic T lymphocytes on hepatoma cell line SMMC-7721 induced by different subsets of dendritic cells in vitro. Hepatobiliary Pancreat Dis Int. 5:422–427. 2006.PubMed/NCBI
26	Olioso P, Giancola R, Di Riti M, Contento A, Accorsi P and Iacone A: Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: A pilot clinical trial. Hematol Oncol. 27:130–139. 2009. View Article : Google Scholar : PubMed/NCBI
27	Qiu YR, Yang CL, Chen LB and Wang Q: Analysis of CD8 (+) and CD8 (+) CD28 (-) cell subsets in patients with hepatocellular carcinoma. Di Yi Jun Yi Da Xue Xue Bao. 22:72–73. 2002.(In Chinese). PubMed/NCBI
28	Shibolet O, Alper R, Zlotogarov L, et al: Suppression of hepatocellular carcinoma growth via oral immune regulation towards tumor-associated antigens is associated with increased NKT and CD8⁺lymphocytes. Oncology. 66:323–330. 2004. View Article : Google Scholar : PubMed/NCBI