Progress in immunotherapy for hepatocellular carcinoma

GUO Lingling; QIU Jinrong

doi:10.3969/j.issn.1006-0111.2017.04.019

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2017 > 35(4): 362-366

GUO Lingling, QIU Jinrong. Progress in immunotherapy for hepatocellular carcinoma[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(4): 362-366. doi: 10.3969/j.issn.1006-0111.2017.04.019

Citation:

GUO Lingling, QIU Jinrong. Progress in immunotherapy for hepatocellular carcinoma[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(4): 362-366. doi: 10.3969/j.issn.1006-0111.2017.04.019

Progress in immunotherapy for hepatocellular carcinoma

doi: 10.3969/j.issn.1006-0111.2017.04.019

Division of Biological Therapies for Cancer, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai 200438, China

Received Date: 2017-01-18
Rev Recd Date: 2017-05-31

Abstract

Hepatocellular carcinoma is a malignant tumor with high morbidity and mortality globally. The therapeutic results on hepatocellular carcinoma with surgery and other classical treatments are not satisfactory. Tumor immunotherapies, such as dendritic cells and cytokine-induced killer cells (DC-CIK), tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor T cells (CAR-T), immune checkpoint blockade (such as PD-1 blockade,CTL4 blockade) etc., are very promising new therapeutic approaches. In this paper, the progresses in the immunotherapy, mainly on PD-1, DC-CIK, TIL, are reviewed. Also pluripotent immune killer cells (PIK) which was developed in our lab was briefly introduced.
- hepatocellular carcinoma,
- tumor immunotherapy,
- DC,
- PD-1 blockade,
- PIK

References

[1]	Torre LA, Bray F, Siegel RL,et al. Global cancer statistics,2012[J]. CA Cancer J Clin,2015,65(2): 87-108.
[2]	Car BI. Hepatocellular carcinoma: current management and future trends[J]. Gastroenterology,2004,127(5 Suppl 1): S218-224.
[3]	Llovet JM, Ricci S, Mazzaferro V,et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med,2008,359(4): 378-390.
[4]	Killock D. Liver cancer: Regorafenib-a new RESORCE in HCC[J]. Nat Rev Clin Oncol, 2017, 14(2): 70-71.
[5]	Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy[J]. Science,2013,342(6165): 1432-1433.
[6]	Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial[J]. Lancet,2014,384(9948): 1109-1117.
[7]	Robert C, Schachter J, Long GV,et al. Pembrolizumab versus ipilimumab in advanced melanoma[J]. N Engl J Med,2015,372(26): 2521-2532.
[8]	Garon EB, Rizvi NA, Hui R,et al. Pembrolizumab for the treatment of non-small-cell lung cancer[J]. N Engl J Med,2015,372(21): 2018-2028.
[9]	Harding JJ, El Dika I, Abou-Alfa GK. Immunotherapy in hepatocellular carcinoma: Primed to make a difference[J]. Cancer,2016,122(3): 367-377.
[10]	Gravitz L. Cancer immunotherapy[J]. Nature, 2013,504(7480): S1.
[11]	Kim HM, Lim J, Yoon YD,et al. Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma[J]. Int Immunopharmacol,2007,7(13): 1793-1801.
[12]	Schmidt-Wolf IG, Negrin RS, Kiem HP,et al. Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity[J]. J Exp Med,1991,174(1): 139-149.
[13]	Banchereau J, Steinman RM. Steinman. Dendritic cells and the control of immunity[J]. Nature,1998, 392(6673): 245-252.
[14]	Zhang L, Zhu W, Li J,et al. Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine-induced killer cell therapy in hepatobiliary and pancreatic cancer[J]. Mol Clin Oncol,2016,4(1): 129-133.
[15]	Lin T, Song C, Chuo DY,et al. Clinical effects of autologous dendritic cells combined with cytokine-induced killer cells followed by chemotherapy in treating patients with advanced colorectal cancer: a prospective study[J]. Tumour Biol,2016,37(4): 4367-4372.
[16]	Wang S, Wang Z. Efficacy and safety of dendritic cells co-cultured with cytokine-induced killer cells immunotherapy for non-small-cell lung cancer[J]. Int Immunopharmacol,2015,28(1): 22-28.
[17]	Jiang JT, Shen YP, Wu CP,et al. Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients[J]. World J Gastroenterol,2010,16(48): 6155-6162.
[18]	Hui D, Qiang L, Jian W,et al. A randomized,controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma[J]. Dig Liver Dis,2009,41(1): 36-41.
[19]	Pan K, Li YQ, Wang W,et al. The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients[J]. Ann Surg Oncol, 2013,20(13): 4305-4311.
[20]	Xie F, Zhang X, Li H,et al. Adoptive immunotherapy in postoperative hepatocellular carcinoma: a systemic review[J]. PLoS One,2012,7(8): e42879.
[21]	Niu LZ, Li JL, Zeng JY,et al. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer[J]. World J Gastroenterol,2013,19(22): 3473-3480.
[22]	Cui J, Wang N, Zhao H,et al. Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma[J]. Int J Cancer,2014,134(2): 342-351.
[23]	Hao MZ, Lin HL, Chen Q,et al. Efficacy of transcatheter arterial chemoembolization combined with cytokine-induced killer cell therapy on hepatocellular carcinoma: a comparative study[J]. Chin J Cancer,2010,29(2): 172-177.
[24]	郭伟伟, 刘莉, 吴德华. DC-CIK细胞免疫治疗联合TACE术治疗原发性肝癌[J]. 南方医科大学学报,2014,34(5): 674-678.
[25]	He G, Zheng C, Huo H,et al. TACE combined with dendritic cells and cytokine-induced killer cells in the treatment of hepatocellular carcinoma: A meta-analysis[J]. Int Immunopharmacol,2016,40: 436-442.
[26]	Rosenberg SA, Restifo NP, Yang JC,et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy[J]. Nat Rev Cancer,2008,8(4): 299-308.
[27]	Shirabe K, Motomura T, Muto J,et al. Tumor-infiltrating lymphocytes and hepatocellular carcinoma: pathology and clinical management[J]. Int J Clin Oncol,2010,15(6): 552-558.
[28]	Jiang SS, Tang Y, Zhang YJ,et al. A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma[J]. Oncotarget,2015,6(38): 41339-41349.
[29]	Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy[J]. Cancer Control,2014,21(3): 231-237.
[30]	Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms,response biomarkers,and combinations[J]. Sci Transl Med,2016, 8(328): 328rv324.
[31]	Wu K, Kryczek I, Chen L,et al. Kupffer cell suppression of CD8⁺ T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions[J]. Cancer Res,2009,69(20): 8067-8075.
[32]	Finkelmeier F, Canli Ö, Tal A,et al. High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis[J]. Eur J Cancer,2016,59: 152-159.
[33]	Gao Q, Wang XY, Qiu SJ,et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma[J]. Clin Cancer Res,2009,15(3): 971-979.
[34]	Kuang DM, Zhao Q, Peng C,et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1[J]. J Exp Med,2009,206(6): 1327-1337.
[35]	Ouyang FZ, Wu RQ, Wei Y,et al. Dendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma[J]. Nat Commun,2016,7: 13453.
[36]	Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer[J]. Nature,2014,515(7528): 558-562.
[37]	Brahmer JR, Tykodi SS, Chow LQ,et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer[J]. N Engl J Med,2012,366(26): 2455-2465.
[38]	Armand P, Nagler A, Weller EA,et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase Ⅱ trial[J]. J Clin Oncol,2013,31(33): 4199-4206.
[39]	Westin JR, Chu F, Zhang M,et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group,open-label,phase 2 trial[J]. Lancet Oncol,2014,15(1): 69-77.
[40]	Ansell SM, Lesokhin AM, Borrello I,et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma[J]. N Engl J Med,2015,372(4): 311-319.
[41]	Herbst RS, Soria JC, Kowanetz M,et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J]. Nature,2014,515(7528): 563-567.
[42]	El-Khoueiry A B, Melero I, Crocenzi T S, et al.Phase Ⅰ/Ⅱ safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040[J]. Clin Oncol 2015,33(18): LBA101.
[43]	Chen CL, Pan QZ, Zhao JJ,et al. PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma[J]. Oncoimmunology,2016,5(7): e1176653.
[44]	Le DT, Uram JN, Wang H,et al. PD-1 blockade in tumors with mismatch-repair deficiency[J]. N Engl J Med,2015,372(26): 2509-2520.
[45]	Sun TW, Gao Q, Qiu SJ,et al. B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence[J]. Cancer Immunol Immunother,2012,61(11): 2171-2182.
[46]	Pan QZ, Wang QJ, Dan JQ,et al. A nomogram for predicting the benefit of adjuvant cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma[J]. Sci Rep,2015,5: 9202.
[47]	Tang H, Qiao J, Fu YX. Immunotherapy and tumor microenvironment[J]. Cancer Lett,2016,370(1): 85-90.
[48]	Sivan A, Corrales L, Hubert N,et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science,2015,350(6264): 1084-1089.
[49]	Vétizou M, Pitt JM, Daillère R,et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science,2015,350(6264): 1079-1084.
[50]	Wang XP, Xu M, Gao HF,et al. Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma[J]. World J Gastroenterol,2013, 19(19): 2956-2962.
[51]	Qiu Y, Xu MB, Yun MM,et al. Hepatocellular carcinoma-specific immunotherapy with synthesized alpha1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells[J]. World J Gastroenterol,2011,17(48): 5260-5266.

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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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Progress in immunotherapy for hepatocellular carcinoma

Division of Biological Therapies for Cancer, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai 200438, China

Received Date: 2017-01-18

Rev Recd Date: 2017-05-31

Key words:

Abstract: Hepatocellular carcinoma is a malignant tumor with high morbidity and mortality globally. The therapeutic results on hepatocellular carcinoma with surgery and other classical treatments are not satisfactory. Tumor immunotherapies, such as dendritic cells and cytokine-induced killer cells (DC-CIK), tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor T cells (CAR-T), immune checkpoint blockade (such as PD-1 blockade,CTL4 blockade) etc., are very promising new therapeutic approaches. In this paper, the progresses in the immunotherapy, mainly on PD-1, DC-CIK, TIL, are reviewed. Also pluripotent immune killer cells (PIK) which was developed in our lab was briefly introduced.

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Reference (51)

[1]	Torre LA, Bray F, Siegel RL,et al. Global cancer statistics,2012[J]. CA Cancer J Clin,2015,65(2): 87-108.
[2]	Car BI. Hepatocellular carcinoma: current management and future trends[J]. Gastroenterology,2004,127(5 Suppl 1): S218-224.
[3]	Llovet JM, Ricci S, Mazzaferro V,et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med,2008,359(4): 378-390.
[4]	Killock D. Liver cancer: Regorafenib-a new RESORCE in HCC[J]. Nat Rev Clin Oncol, 2017, 14(2): 70-71.
[5]	Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy[J]. Science,2013,342(6165): 1432-1433.
[6]	Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial[J]. Lancet,2014,384(9948): 1109-1117.
[7]	Robert C, Schachter J, Long GV,et al. Pembrolizumab versus ipilimumab in advanced melanoma[J]. N Engl J Med,2015,372(26): 2521-2532.
[8]	Garon EB, Rizvi NA, Hui R,et al. Pembrolizumab for the treatment of non-small-cell lung cancer[J]. N Engl J Med,2015,372(21): 2018-2028.
[9]	Harding JJ, El Dika I, Abou-Alfa GK. Immunotherapy in hepatocellular carcinoma: Primed to make a difference[J]. Cancer,2016,122(3): 367-377.
[10]	Gravitz L. Cancer immunotherapy[J]. Nature, 2013,504(7480): S1.
[11]	Kim HM, Lim J, Yoon YD,et al. Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma[J]. Int Immunopharmacol,2007,7(13): 1793-1801.
[12]	Schmidt-Wolf IG, Negrin RS, Kiem HP,et al. Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity[J]. J Exp Med,1991,174(1): 139-149.
[13]	Banchereau J, Steinman RM. Steinman. Dendritic cells and the control of immunity[J]. Nature,1998, 392(6673): 245-252.
[14]	Zhang L, Zhu W, Li J,et al. Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine-induced killer cell therapy in hepatobiliary and pancreatic cancer[J]. Mol Clin Oncol,2016,4(1): 129-133.
[15]	Lin T, Song C, Chuo DY,et al. Clinical effects of autologous dendritic cells combined with cytokine-induced killer cells followed by chemotherapy in treating patients with advanced colorectal cancer: a prospective study[J]. Tumour Biol,2016,37(4): 4367-4372.
[16]	Wang S, Wang Z. Efficacy and safety of dendritic cells co-cultured with cytokine-induced killer cells immunotherapy for non-small-cell lung cancer[J]. Int Immunopharmacol,2015,28(1): 22-28.
[17]	Jiang JT, Shen YP, Wu CP,et al. Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients[J]. World J Gastroenterol,2010,16(48): 6155-6162.
[18]	Hui D, Qiang L, Jian W,et al. A randomized,controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma[J]. Dig Liver Dis,2009,41(1): 36-41.
[19]	Pan K, Li YQ, Wang W,et al. The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients[J]. Ann Surg Oncol, 2013,20(13): 4305-4311.
[20]	Xie F, Zhang X, Li H,et al. Adoptive immunotherapy in postoperative hepatocellular carcinoma: a systemic review[J]. PLoS One,2012,7(8): e42879.
[21]	Niu LZ, Li JL, Zeng JY,et al. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer[J]. World J Gastroenterol,2013,19(22): 3473-3480.
[22]	Cui J, Wang N, Zhao H,et al. Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma[J]. Int J Cancer,2014,134(2): 342-351.
[23]	Hao MZ, Lin HL, Chen Q,et al. Efficacy of transcatheter arterial chemoembolization combined with cytokine-induced killer cell therapy on hepatocellular carcinoma: a comparative study[J]. Chin J Cancer,2010,29(2): 172-177.
[24]	郭伟伟, 刘莉, 吴德华. DC-CIK细胞免疫治疗联合TACE术治疗原发性肝癌[J]. 南方医科大学学报,2014,34(5): 674-678.
[25]	He G, Zheng C, Huo H,et al. TACE combined with dendritic cells and cytokine-induced killer cells in the treatment of hepatocellular carcinoma: A meta-analysis[J]. Int Immunopharmacol,2016,40: 436-442.
[26]	Rosenberg SA, Restifo NP, Yang JC,et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy[J]. Nat Rev Cancer,2008,8(4): 299-308.
[27]	Shirabe K, Motomura T, Muto J,et al. Tumor-infiltrating lymphocytes and hepatocellular carcinoma: pathology and clinical management[J]. Int J Clin Oncol,2010,15(6): 552-558.
[28]	Jiang SS, Tang Y, Zhang YJ,et al. A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma[J]. Oncotarget,2015,6(38): 41339-41349.
[29]	Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy[J]. Cancer Control,2014,21(3): 231-237.
[30]	Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms,response biomarkers,and combinations[J]. Sci Transl Med,2016, 8(328): 328rv324.
[31]	Wu K, Kryczek I, Chen L,et al. Kupffer cell suppression of CD8⁺ T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions[J]. Cancer Res,2009,69(20): 8067-8075.
[32]	Finkelmeier F, Canli Ö, Tal A,et al. High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis[J]. Eur J Cancer,2016,59: 152-159.
[33]	Gao Q, Wang XY, Qiu SJ,et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma[J]. Clin Cancer Res,2009,15(3): 971-979.
[34]	Kuang DM, Zhao Q, Peng C,et al. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1[J]. J Exp Med,2009,206(6): 1327-1337.
[35]	Ouyang FZ, Wu RQ, Wei Y,et al. Dendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma[J]. Nat Commun,2016,7: 13453.
[36]	Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer[J]. Nature,2014,515(7528): 558-562.
[37]	Brahmer JR, Tykodi SS, Chow LQ,et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer[J]. N Engl J Med,2012,366(26): 2455-2465.
[38]	Armand P, Nagler A, Weller EA,et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase Ⅱ trial[J]. J Clin Oncol,2013,31(33): 4199-4206.
[39]	Westin JR, Chu F, Zhang M,et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group,open-label,phase 2 trial[J]. Lancet Oncol,2014,15(1): 69-77.
[40]	Ansell SM, Lesokhin AM, Borrello I,et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma[J]. N Engl J Med,2015,372(4): 311-319.
[41]	Herbst RS, Soria JC, Kowanetz M,et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J]. Nature,2014,515(7528): 563-567.
[42]	El-Khoueiry A B, Melero I, Crocenzi T S, et al.Phase Ⅰ/Ⅱ safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040[J]. Clin Oncol 2015,33(18): LBA101.
[43]	Chen CL, Pan QZ, Zhao JJ,et al. PD-L1 expression as a predictive biomarker for cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma[J]. Oncoimmunology,2016,5(7): e1176653.
[44]	Le DT, Uram JN, Wang H,et al. PD-1 blockade in tumors with mismatch-repair deficiency[J]. N Engl J Med,2015,372(26): 2509-2520.
[45]	Sun TW, Gao Q, Qiu SJ,et al. B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence[J]. Cancer Immunol Immunother,2012,61(11): 2171-2182.
[46]	Pan QZ, Wang QJ, Dan JQ,et al. A nomogram for predicting the benefit of adjuvant cytokine-induced killer cell immunotherapy in patients with hepatocellular carcinoma[J]. Sci Rep,2015,5: 9202.
[47]	Tang H, Qiao J, Fu YX. Immunotherapy and tumor microenvironment[J]. Cancer Lett,2016,370(1): 85-90.
[48]	Sivan A, Corrales L, Hubert N,et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science,2015,350(6264): 1084-1089.
[49]	Vétizou M, Pitt JM, Daillère R,et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science,2015,350(6264): 1079-1084.
[50]	Wang XP, Xu M, Gao HF,et al. Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma[J]. World J Gastroenterol,2013, 19(19): 2956-2962.
[51]	Qiu Y, Xu MB, Yun MM,et al. Hepatocellular carcinoma-specific immunotherapy with synthesized alpha1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells[J]. World J Gastroenterol,2011,17(48): 5260-5266.

Message Board

Progress in immunotherapy for hepatocellular carcinoma

doi: 10.3969/j.issn.1006-0111.2017.04.019

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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