Recent advances of programmed death receptor protein 1 monoclonal antibody therapy in patients with recurrent liver cancer after liver transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

TANG Wei , QIU Jianguo ,  DU Chengyou

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China;

Corresponding author：

DU Chengyou, Email: duchengyou@126.com

Keywords：

programmed death receptor protein-1; monoclonal antibody; checkpoint inhibitor; liver transplantation; immunotherapy; acute graft rejection

DOI：

10.7507/1007-9424.201903097

Video：

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Objective To investigate feasibility, safety, and problems to be solved in treatment with programmed death receptor protein-1 (PD-1) monoclonal antibody for patients with recurrent liver cancer after liver transplantation (LT).Method All of the domestic and foreign cases reports about the application of PD-1 monoclonal antibody in the patients with recurrent liver cancer after the LT were analyzed and summarized.Results In six patients with recurrent liver cancer after the LT who received the PD-1 monoclonal antibody, the acute graft rejections were observed in 3 patients, 2 patients had the progressive disease but there was no evidence of the graft rejection, 1 patient achieved the complete response and there was no evidence of graft rejection and no side effects.Conclusions At present, effect of PD-1 monoclonal antibody therapy is still not sure in patients with recurrent liver cancer after LT. If PD-1 monoclonal antibody is used off-label, close surveillance is needed to discovery possible acute graft rejection.

Citation： TANG Wei, QIU Jianguo, DU Chengyou. Recent advances of programmed death receptor protein 1 monoclonal antibody therapy in patients with recurrent liver cancer after liver transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(9): 1122-1125. doi: 10.7507/1007-9424.201903097 Copy

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2.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3.	万赤丹, 王国斌. 原发性肝癌治疗进展. 腹部外科, 2019, 32(1): 1-6, 22.
4.	王春平, 任波, 陆荫英, 等. 原发性肝癌诊疗规范(2017年版)更新解读. 传染病信息, 2017, 30(4): 193-196, 202.
5.	曲建慧, 张翠红, 李若然, 等. 肝细胞癌免疫治疗的现状与挑战. 传染病信息, 2016, 29(4): 193-197, 208.
6.	郭静, 曲鑫建, 伍会健. 肿瘤免疫疗法中免疫检查点的研究进展. 生理科学进展, 2017, 48(4): 287-293.
7.	Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 2012, 12(4): 252-264.
8.	Bachy E, Coiffier B. Anti-PD1 antibody: a new approach to treatment of lymphomas. Lancet Oncol, 2014, 15(1): 7-8.
9.	Gunturi A, McDermott DF. Potential of new therapies like anti-PD1 in kidney cancer. Curr Treat Options Oncol, 2014, 15(1): 137-146.
10.	Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J, 1992, 11(11): 3887-3895.
11.	郭国宁, 谢谆怡, 陈永文. 共抑制分子PD-1的研究进展. 免疫学杂志, 2010, 26(7): 639-642.
12.	Fife BT, Pauken KE, Eagar TN, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol, 2009, 10(11): 1185-1192.
13.	Liang SC, Latchman YE, Buhlmann JE, et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol, 2003, 33(10): 2706-2716.
14.	Kataoka TR, Fujimoto M, Moriyoshi K, et al. PD-1 regulates the growth of human mastocytosis cells. Allergol Int, 2013, 62(1): 99-104.
15.	Yamazaki T, Akiba H, Iwai H, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol, 2002, 169(10): 5538-5545.
16.	Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008, 26: 677-704.
17.	Zhong X, Tumang JR, Gao W, et al. PD-L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V(H)11/V(H)12 and phosphatidylcholine binding. Eur J Immunol, 2007, 37(9): 2405-2410.
18.	Chambers CA. The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol, 2001, 22(4): 217-223.
19.	Dong H, Chen L. B7-H1 pathway and its role in the evasion of tumor immunity. J Mol Med (Berl), 2003, 81(5): 281-287.
20.	Guan X, Wang H, Ma F, et al. The efficacy and safety of programmed cell death 1 and programmed cell death 1 ligand inhibitors for advanced melanoma: a meta-analysis of clinical trials following the PRISMA guidelines. Medicine (Baltimore), 2016, 95(11): e3134.
21.	Anthony B. PhaseⅠ/Ⅱ safety and antitumor activity of Nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. J Clin Oncol, 2015, 33(18_suppl): LBA101.
22.	王征, 周俭. 中国肝癌肝移植现状及展望. 实用器官移植电子杂志, 2019, 7(1): 1-3.
23.	李坚, 王洪林. 肝癌肝移植术后肝癌复发的研究进展. 中华外科杂志, 2005, 43(11): 753-756.
24.	Zimmerman MA, Ghobrial RM, Tong MJ, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg, 2008, 143(2): 182-188.
25.	Wang ZY, Geng L, Zheng SS. Current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation. Hepatobiliary Pancreat Dis Int, 2015, 14(2): 145-149.
26.	Friend BD, Venick RS, McDiarmid SV, et al. Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma. Pediatr Blood Cancer, 2017, 64(12): e26682.
27.	Varkaris A, Lewis DW, Nugent FW. Preserved liver transplant after PD-1 pathway inhibitor for hepatocellular carcinoma. Am J Gastroenterol, 2017, 112(12): 1895-1896.
28.	Rammohan A, Reddy MS, Farouk M, et al. Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: The silver bullet? Hepatology, 2018, 67(3): 1166-1168.
29.	De Toni EN, Gerbes AL. Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient. Gastroenterology, 2017, 152(6): 1631-1633.
30.	汪国营, 唐晖, 张英才, 等. 程序性死亡受体(PD)-1单克隆抗体治疗肝癌肝移植术后复发诱发急性免疫性肝炎: 附1例报告. 器官移植, 2016, 7(1): 44-47.
31.	Kudo M. Immune checkpoint blockade in hepatocellular carcinoma: 2017 Update. Liver Cancer, 2016, 6(1): 1-12.
32.	Wanchoo R, Riella LV, Uppal NN, et al. Immune checkpoint inhibitors in the cancer patient with an organ transplant. J Onco Nephrol, 2017, 1: 42-48.
33.	Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol, 2007, 19(7): 813-824.
34.	Riella LV, Paterson AM, Sharpe AH, et al. Role of the PD-1 pathway in the immune response. Am J Transplant, 2012, 12(10): 2575-2587.
35.	Barnett R, Barta VS, Jhaveri KD. Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab. N Engl J Med, 2017, 376(2): 191-192.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. 万赤丹, 王国斌. 原发性肝癌治疗进展. 腹部外科, 2019, 32(1): 1-6, 22.
4. 王春平, 任波, 陆荫英, 等. 原发性肝癌诊疗规范(2017年版)更新解读. 传染病信息, 2017, 30(4): 193-196, 202.
5. 曲建慧, 张翠红, 李若然, 等. 肝细胞癌免疫治疗的现状与挑战. 传染病信息, 2016, 29(4): 193-197, 208.
6. 郭静, 曲鑫建, 伍会健. 肿瘤免疫疗法中免疫检查点的研究进展. 生理科学进展, 2017, 48(4): 287-293.
7. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 2012, 12(4): 252-264.
8. Bachy E, Coiffier B. Anti-PD1 antibody: a new approach to treatment of lymphomas. Lancet Oncol, 2014, 15(1): 7-8.
9. Gunturi A, McDermott DF. Potential of new therapies like anti-PD1 in kidney cancer. Curr Treat Options Oncol, 2014, 15(1): 137-146.
10. Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J, 1992, 11(11): 3887-3895.
11. 郭国宁, 谢谆怡, 陈永文. 共抑制分子PD-1的研究进展. 免疫学杂志, 2010, 26(7): 639-642.
12. Fife BT, Pauken KE, Eagar TN, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol, 2009, 10(11): 1185-1192.
13. Liang SC, Latchman YE, Buhlmann JE, et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol, 2003, 33(10): 2706-2716.
14. Kataoka TR, Fujimoto M, Moriyoshi K, et al. PD-1 regulates the growth of human mastocytosis cells. Allergol Int, 2013, 62(1): 99-104.
15. Yamazaki T, Akiba H, Iwai H, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol, 2002, 169(10): 5538-5545.
16. Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008, 26: 677-704.
17. Zhong X, Tumang JR, Gao W, et al. PD-L2 expression extends beyond dendritic cells/macrophages to B1 cells enriched for V(H)11/V(H)12 and phosphatidylcholine binding. Eur J Immunol, 2007, 37(9): 2405-2410.
18. Chambers CA. The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol, 2001, 22(4): 217-223.
19. Dong H, Chen L. B7-H1 pathway and its role in the evasion of tumor immunity. J Mol Med (Berl), 2003, 81(5): 281-287.
20. Guan X, Wang H, Ma F, et al. The efficacy and safety of programmed cell death 1 and programmed cell death 1 ligand inhibitors for advanced melanoma: a meta-analysis of clinical trials following the PRISMA guidelines. Medicine (Baltimore), 2016, 95(11): e3134.
21. Anthony B. PhaseⅠ/Ⅱ safety and antitumor activity of Nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. J Clin Oncol, 2015, 33(18_suppl): LBA101.
22. 王征, 周俭. 中国肝癌肝移植现状及展望. 实用器官移植电子杂志, 2019, 7(1): 1-3.
23. 李坚, 王洪林. 肝癌肝移植术后肝癌复发的研究进展. 中华外科杂志, 2005, 43(11): 753-756.
24. Zimmerman MA, Ghobrial RM, Tong MJ, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg, 2008, 143(2): 182-188.
25. Wang ZY, Geng L, Zheng SS. Current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation. Hepatobiliary Pancreat Dis Int, 2015, 14(2): 145-149.
26. Friend BD, Venick RS, McDiarmid SV, et al. Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma. Pediatr Blood Cancer, 2017, 64(12): e26682.
27. Varkaris A, Lewis DW, Nugent FW. Preserved liver transplant after PD-1 pathway inhibitor for hepatocellular carcinoma. Am J Gastroenterol, 2017, 112(12): 1895-1896.
28. Rammohan A, Reddy MS, Farouk M, et al. Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: The silver bullet? Hepatology, 2018, 67(3): 1166-1168.
29. De Toni EN, Gerbes AL. Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient. Gastroenterology, 2017, 152(6): 1631-1633.
30. 汪国营, 唐晖, 张英才, 等. 程序性死亡受体(PD)-1单克隆抗体治疗肝癌肝移植术后复发诱发急性免疫性肝炎: 附1例报告. 器官移植, 2016, 7(1): 44-47.
31. Kudo M. Immune checkpoint blockade in hepatocellular carcinoma: 2017 Update. Liver Cancer, 2016, 6(1): 1-12.
32. Wanchoo R, Riella LV, Uppal NN, et al. Immune checkpoint inhibitors in the cancer patient with an organ transplant. J Onco Nephrol, 2017, 1: 42-48.
33. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol, 2007, 19(7): 813-824.
34. Riella LV, Paterson AM, Sharpe AH, et al. Role of the PD-1 pathway in the immune response. Am J Transplant, 2012, 12(10): 2575-2587.
35. Barnett R, Barta VS, Jhaveri KD. Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab. N Engl J Med, 2017, 376(2): 191-192.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Recent advances of programmed death receptor protein 1 monoclonal antibody therapy in patients with recurrent liver cancer after liver transplantation

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