Abstract
The discovery of the immune checkpoint inhibitors such as programed cell death-1 protein/ Programmed death ligand-1 or 2 and (PD-1/PD-L1 or PD-L2) and Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) paved the way for developing novel cancer treatment. The check point inhibitors are found to be very efficient in treating many hot tumors (with immune environment) such as bladder cancer, melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), etc. Numerous clinical trials have been initiated to evaluate the safety and effectiveness of immune checkpoint inhibitors for patients with different cancer types, including hepatocellular carcinoma (HCC), pancreatic and prostate cancer. The results and findings of these trials are highly appreciated. However, the search for check point inhibitors with better efficacy for the treatment of HCC is still going on. The present review focuses on advancement in HCC treatments with respect to various standard therapies and immunotherapy.
Keywords: HCC, PD-1 inhibitors, CTLA-4 inhibitors, GITR, LAG-3, sorafenib, TACE.
Graphical Abstract
[http://dx.doi.org/10.3748/wjg.v13.i17.2455] [PMID: 17552029]
[http://dx.doi.org/10.1053/j.gastro.2011.12.061] [PMID: 22537432]
[http://dx.doi.org/10.2217/hep-2017-0024] [PMID: 30302194]
[http://dx.doi.org/10.20517/2394-5079.2018.87] [PMID: 30687780]
[http://dx.doi.org/10.7150/ijbs.7.651] [PMID: 21647333]
[http://dx.doi.org/10.1016/j.cytogfr.2014.07.014] [PMID: 25156420]
[http://dx.doi.org/10.1016/j.smim.2008.07.001] [PMID: 18684640]
[http://dx.doi.org/10.1097/COC.0000000000000239] [PMID: 26558876]
[http://dx.doi.org/10.1186/s13046-019-1259-z] [PMID: 31196207]
[http://dx.doi.org/10.3389/fphar.2017.00561] [PMID: 28878676]
[http://dx.doi.org/10.1097/PPO.0000000000000303] [PMID: 29360728]
[http://dx.doi.org/10.3390/cancers11101554] [PMID: 31615069]
[http://dx.doi.org/10.1084/jem.20161462] [PMID: 27903604]
[http://dx.doi.org/10.1038/sigtrans.2016.29] [PMID: 29263905]
[http://dx.doi.org/10.1016/j.immuni.2013.07.012] [PMID: 23890059]
[http://dx.doi.org/10.3748/wjg.v20.i15.4115] [PMID: 24764650]
[http://dx.doi.org/10.1200/JCO.2006.09.4565] [PMID: 17577038]
[http://dx.doi.org/10.1159/000485471] [PMID: 29662837]
[http://dx.doi.org/10.1053/jhep.2003.50047] [PMID: 12540794]
[http://dx.doi.org/10.1016/j.ctrv.2018.11.002] [PMID: 30447470]
[http://dx.doi.org/10.3348/kjr.2009.10.5.425] [PMID: 19721826]
[http://dx.doi.org/10.1055/s-0033-1333648] [PMID: 24436512]
[http://dx.doi.org/10.1007/s00270-011-0287-7] [PMID: 22009576]
[http://dx.doi.org/10.1186/s12885-019-5989-2] [PMID: 31409405]
[http://dx.doi.org/10.3748/wjg.v21.i21.6518] [PMID: 26074690]
[http://dx.doi.org/10.1016/j.jvir.2013.01.075]
[http://dx.doi.org/10.1186/s40425-019-0749-z] [PMID: 31627733]
[http://dx.doi.org/10.1155/2018/8740976] [PMID: 29785403]
[http://dx.doi.org/10.3748/wjg.v25.i24.2977] [PMID: 31293335]
[http://dx.doi.org/10.1016/j.jhep.2015.02.038] [PMID: 25733155]
[http://dx.doi.org/10.1002/hep.27246] [PMID: 24912948]
[http://dx.doi.org/10.1038/nrgastro.2015.173] [PMID: 26484443]
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[http://dx.doi.org/10.1016/j.jhep.2016.10.029] [PMID: 27816492]
[http://dx.doi.org/10.1016/j.jhep.2013.02.022] [PMID: 23466307]
[http://dx.doi.org/10.1002/ijc.25397] [PMID: 20473887]
[http://dx.doi.org/10.1084/jem.20082173] [PMID: 19451266]
[http://dx.doi.org/10.3389/fonc.2018.00086] [PMID: 29644214]
[http://dx.doi.org/10.1126/science.271.5256.1734] [PMID: 8596936]
[http://dx.doi.org/10.2217/hep-2016-0004] [PMID: 30191042]
[http://dx.doi.org/10.4110/in.2020.20.e11] [PMID: 32158599]
[http://dx.doi.org/10.1016/j.jhep.2017.09.007] [PMID: 28923358]
[http://dx.doi.org/10.1186/s40425-019-0824-5] [PMID: 31783782]
[http://dx.doi.org/10.1159/000503254] [PMID: 32479569]
[http://dx.doi.org/10.1038/ni1271] [PMID: 16286920]
[http://dx.doi.org/10.1186/s13045-018-0667-4] [PMID: 30309387]
[http://dx.doi.org/10.1002/med.20249] [PMID: 21793015]
[http://dx.doi.org/10.1002/hep.25777] [PMID: 22505239]
[http://dx.doi.org/10.1016/S0959-8049(16)32903-3]
[http://dx.doi.org/10.1038/s41598-019-47235-z] [PMID: 31337865]
[http://dx.doi.org/10.1111/imr.12520] [PMID: 28258697]
[http://dx.doi.org/10.1016/j.cell.2008.07.001] [PMID: 18662538]
[http://dx.doi.org/10.1016/S1097-2765(03)00386-1] [PMID: 14580334]
[http://dx.doi.org/10.3390/cancers12020339] [PMID: 32028632]
[PMID: 27340590]
[http://dx.doi.org/10.1007/s10555-006-9006-2] [PMID: 16951986]
[http://dx.doi.org/10.1371/journal.pone.0222259] [PMID: 32210440]
[http://dx.doi.org/10.14309/ctg.0000000000000056] [PMID: 31295152]
[http://dx.doi.org/10.2174/138161212802430431] [PMID: 22630081]
[http://dx.doi.org/10.1084/jem.171.5.1393] [PMID: 1692078]
[http://dx.doi.org/10.1038/ni.1679] [PMID: 19043418]
[http://dx.doi.org/10.1073/pnas.1003345107] [PMID: 20385810]
[http://dx.doi.org/10.1016/j.imlet.2012.12.004] [PMID: 23261718]
[PMID: 30603054]
[http://dx.doi.org/10.1002/hep.26013] [PMID: 22911397]
[http://dx.doi.org/10.1002/ijc.32181] [PMID: 30719701]
[http://dx.doi.org/10.1186/s40425-017-0266-x] [PMID: 28807056]
[http://dx.doi.org/10.1002/cncr.30491] [PMID: 28543698]
[PMID: 3893689]
[http://dx.doi.org/10.18632/oncotarget.15454] [PMID: 28412743]
[http://dx.doi.org/10.3389/fonc.2019.00248] [PMID: 31024850]
[http://dx.doi.org/10.3389/fimmu.2019.00661] [PMID: 30984204]
[http://dx.doi.org/10.21037/atm.2016.04.01] [PMID: 27563648]
[http://dx.doi.org/10.3389/fonc.2019.00019] [PMID: 30719425]
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.TPS4146]
[http://dx.doi.org/10.1038/s41541-019-0103-y] [PMID: 30774998]
[http://dx.doi.org/10.1056/NEJMoa1504030] [PMID: 26027431]
[http://dx.doi.org/10.1159/000452138] [PMID: 28275577]
[http://dx.doi.org/10.1159/000486487] [PMID: 29662830]
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.4073]
[http://dx.doi.org/10.1159/000496277] [PMID: 30815391]
[http://dx.doi.org/10.1200/JCO.2018.36.15_suppl.4076]