A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 03 2020
04 03 2020
Historique:
received:
19
11
2019
accepted:
12
02
2020
entrez:
6
3
2020
pubmed:
7
3
2020
medline:
11
11
2020
Statut:
epublish
Résumé
α-Fetoprotein (AFP) is considered a good target for immunotherapy strategies against hepatocellular carcinoma (HCC); however, no immunodominant AFP-derived MHC class II-restricted helper T-lymphocyte (HTL) epitope has been reported. Therefore, we identified novel AFP-derived HTL epitopes possessing high immunogenicity. HTL epitopes were predicted using the online service, and peptides were subsequently synthesized. Four newly synthesized peptides showed positive reactivity in >20% patients on ELISPOT using peripheral blood mononuclear cells (PBMCs). Among these, the highest rate was shown by AFP
Identifiants
pubmed: 32132566
doi: 10.1038/s41598-020-60843-4
pii: 10.1038/s41598-020-60843-4
pmc: PMC7055302
doi:
Substances chimiques
Epitopes, T-Lymphocyte
0
Neoplasm Proteins
0
Peptides
0
alpha-Fetoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4021Références
Torre, L. A. et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87–108 (2015).
doi: 10.3322/caac.21262
Bosch, F. X., Ribes, J., Díaz, M. & Cléries, R. Primary liver cancer: Worldwide incidence and trends. Gastroenterology. 127, S5–S16 (2004).
doi: 10.1053/j.gastro.2004.09.011
Bruix, J. & Sherman, M. American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 53, 1020–1022 (2011).
doi: 10.1002/hep.24199
Heimbach, J. K. et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 67, 358–380 (2018).
doi: 10.1002/hep.29086
Llovet, J. M. et al. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).
doi: 10.1056/NEJMoa0708857
Bruix, J. et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 389, 56–66 (2017).
doi: 10.1016/S0140-6736(16)32453-9
Kudo, M. et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 391, 1163–1173 (2018).
doi: 10.1016/S0140-6736(18)30207-1
Abou-Alfa, G. K. et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N. Engl. J. Med. 379, 54–63 (2018).
doi: 10.1056/NEJMoa1717002
Johnson, P. J. Role of alpha-fetoprotein in the diagnosis and management of hepatocellular carcinoma. J. Gastroenterol. Hepatol. 14(Suppl), S32–S36 (1999).
doi: 10.1046/j.1440-1746.1999.01873.x
Butterfield, L. H. et al. A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin. Cancer Res. 12, 2817–2825 (2006).
doi: 10.1158/1078-0432.CCR-05-2856
Sun, Z. et al. Status of and prospects for cancer vaccines against hepatocellular carcinoma in clinical trials. Biosci. Trends. 10, 85–91 (2016).
doi: 10.5582/bst.2015.01128
Mizukoshi, E., Nakamoto, Y., Tsuji, H., Yamashita, T. & Kaneko, S. Identification of alpha-fetoprotein-derived peptides recognized by cytotoxic T lymphocytes in HLA-A24+ patients with hepatocellular carcinoma. Int. J. Cancer. 118, 1194–1204 (2006).
doi: 10.1002/ijc.21468
Nakagawa, H. et al. Association between high-avidity T-cell receptors, induced by alpha-fetoprotein-derived peptides, and anti-tumor effects in patients with hepatocellular carcinoma. Gastroenterology. 152, 1395–1406 e1310 (2017).
doi: 10.1053/j.gastro.2017.02.001
Bevan, M. J. Helping the CD8(+) T-cell response. Nat. Rev. Immunol. 4, 595–602 (2004).
doi: 10.1038/nri1413
Borst, J., Ahrends, T., Babala, N., Melief, C. J. M. & Kastenmuller, W. CD4(+) T cell help in cancer immunology and immunotherapy. Nat. Rev. Immunol. 18, 635–647 (2018).
doi: 10.1038/s41577-018-0044-0
Koido, S. et al. Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms’ tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer. Clin. Cancer Res. 20, 4228–4239 (2014).
doi: 10.1158/1078-0432.CCR-14-0314
Alisa, A. et al. Analysis of CD4+ T-Cell responses to a novel alpha-fetoprotein-derived epitope in hepatocellular carcinoma patients. Clin. Cancer Res. 11, 6686–6694 (2005).
doi: 10.1158/1078-0432.CCR-05-0382
Ayaru, L. et al. Unmasking of α-fetoprotein-specific CD4+ T cell responses in hepatocellular carcinoma patients undergoing embolization. J. Immunol. 178, 1914–1922 (2007).
doi: 10.4049/jimmunol.178.3.1914
Alisa, A. et al. Human CD4+ T cells recognize an epitope within-fetoprotein sequence and develop into TGF–producing CD4+ T cells. J. Immunol. 180, 5109–5117 (2008).
doi: 10.4049/jimmunol.180.7.5109
Kim, J. et al. In vitro binding analysis of hepatitis B virus preS-derived putative helper T-cell epitopes to MHC class II molecules using stable HLA-DRB1*0405/DRA*0101 transfected cells. IUBMB Life. 50, 379–384 (2000).
doi: 10.1080/713803746
Ikeda, N. et al. Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study. Tissue Antigens 85, 252–259 (2015).
doi: 10.1111/tan.12536
Kumagai, M. et al. Immune response to human telomerase reverse transcriptase-derived helper T cell epitopes in hepatocellular carcinoma patients. Liver Int. 38, 1635–1645 (2018).
doi: 10.1111/liv.13713
Witkowski, M. et al. Lack of ex vivo peripheral and intrahepatic alpha-fetoprotein-specific CD4+ responses in hepatocellular carcinoma. Int. J. Cancer. 129, 2171–2182 (2011).
doi: 10.1002/ijc.25866
Butterfield, L. H. et al. T cell responses to HLA-A*0201-restricted peptides derived from human fetoprotein. J. Immunol. 166, 5300–5308 (2001).
doi: 10.4049/jimmunol.166.8.5300
Evdokimova, V. N., Liu, Y., Potter, D. M. & Butterfield, L. H. AFP-specific CD4+ helper T-cell responses in healthy donors and HCC patients. J. Immunother. 30, 425–437 (2007).
doi: 10.1097/CJI.0b013e31802fd8e2
Mellman, I., Coukos, G. & Dranoff, G. Cancer immunotherapy comes of age. Nature. 480, 480–489 (2011).
doi: 10.1038/nature10673
Pardee, A. D., Shi, J. & Butterfield, L. H. Tumor-derived alpha-fetoprotein impairs the differentiation and T cell stimulatory activity of human dendritic cells. J. Immunol. 193, 5723–5732 (2014).
doi: 10.4049/jimmunol.1400725
Mizukoshi, E. et al. Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma. Hepatology. 57, 1448–1457 (2013).
doi: 10.1002/hep.26153
Zerbini, A. et al. Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res. 66, 1139–1146 (2006).
doi: 10.1158/0008-5472.CAN-05-2244