Cargando…

Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC), one of the deadliest gastrointestinal cancers, has had limited effective therapeutic strategies up to now. Accumulating evidence suggests that effective immunotherapy in cancer patients has been associated with T cells responsive to mutant peptides derived...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Zhiwei, Ran, Ling, Chen, Chunxia, Shi, Ranran, Dong, Yu, Li, Yubing, Zhou, Xiuman, Qi, Yuanming, Zhu, Pingping, Gao, Yanfeng, Wu, Yahong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541546/
https://www.ncbi.nlm.nih.gov/pubmed/34696226
http://dx.doi.org/10.3390/vaccines9101118
_version_ 1784589257005858816
author Wang, Zhiwei
Ran, Ling
Chen, Chunxia
Shi, Ranran
Dong, Yu
Li, Yubing
Zhou, Xiuman
Qi, Yuanming
Zhu, Pingping
Gao, Yanfeng
Wu, Yahong
author_facet Wang, Zhiwei
Ran, Ling
Chen, Chunxia
Shi, Ranran
Dong, Yu
Li, Yubing
Zhou, Xiuman
Qi, Yuanming
Zhu, Pingping
Gao, Yanfeng
Wu, Yahong
author_sort Wang, Zhiwei
collection PubMed
description Esophageal squamous cell carcinoma (ESCC), one of the deadliest gastrointestinal cancers, has had limited effective therapeutic strategies up to now. Accumulating evidence suggests that effective immunotherapy in cancer patients has been associated with T cells responsive to mutant peptides derived from neoantigens. Here, we selected 35 human leukocyte antigen-A2 (HLA-A2)-restricted mutant (MUT) peptides stemmed from neoantigens of ESCC. Among them, seven mutant peptides had potent binding affinity to HLA-A*0201 molecules and could form a stable peptide/HLA-A*0201 complex. Three mutant peptides (TP53-R267P, NFE2L2-D13N, and PCLO-E4090Q) of those were immunogenic and could induce the cytotoxic T lymphocytes (CTLs) recognizing mutant peptides presented on transfected cells in an HLA-A2-restricted and MUT peptide-specific manner. In addition, the CTL response in immunized HLA-A2.1/K(b) transgenic (Tg) mice was enhanced by coupling MUT peptides to peptide WH, a peptide delivery carrier targeting Clec9a(+) DCs. Then, the possible binding model conversions between the WT and MUT candidate peptides were analyzed by docking with the pockets of HLA-A*0201 molecule. We therefore propose a novel strategy and epitopes for immunotherapy of ESCC based on neoantigens.
format Online
Article
Text
id pubmed-8541546
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85415462021-10-24 Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma Wang, Zhiwei Ran, Ling Chen, Chunxia Shi, Ranran Dong, Yu Li, Yubing Zhou, Xiuman Qi, Yuanming Zhu, Pingping Gao, Yanfeng Wu, Yahong Vaccines (Basel) Article Esophageal squamous cell carcinoma (ESCC), one of the deadliest gastrointestinal cancers, has had limited effective therapeutic strategies up to now. Accumulating evidence suggests that effective immunotherapy in cancer patients has been associated with T cells responsive to mutant peptides derived from neoantigens. Here, we selected 35 human leukocyte antigen-A2 (HLA-A2)-restricted mutant (MUT) peptides stemmed from neoantigens of ESCC. Among them, seven mutant peptides had potent binding affinity to HLA-A*0201 molecules and could form a stable peptide/HLA-A*0201 complex. Three mutant peptides (TP53-R267P, NFE2L2-D13N, and PCLO-E4090Q) of those were immunogenic and could induce the cytotoxic T lymphocytes (CTLs) recognizing mutant peptides presented on transfected cells in an HLA-A2-restricted and MUT peptide-specific manner. In addition, the CTL response in immunized HLA-A2.1/K(b) transgenic (Tg) mice was enhanced by coupling MUT peptides to peptide WH, a peptide delivery carrier targeting Clec9a(+) DCs. Then, the possible binding model conversions between the WT and MUT candidate peptides were analyzed by docking with the pockets of HLA-A*0201 molecule. We therefore propose a novel strategy and epitopes for immunotherapy of ESCC based on neoantigens. MDPI 2021-10-01 /pmc/articles/PMC8541546/ /pubmed/34696226 http://dx.doi.org/10.3390/vaccines9101118 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Zhiwei
Ran, Ling
Chen, Chunxia
Shi, Ranran
Dong, Yu
Li, Yubing
Zhou, Xiuman
Qi, Yuanming
Zhu, Pingping
Gao, Yanfeng
Wu, Yahong
Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
title Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
title_full Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
title_fullStr Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
title_full_unstemmed Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
title_short Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
title_sort identification of hla-a2-restricted mutant epitopes from neoantigens of esophageal squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541546/
https://www.ncbi.nlm.nih.gov/pubmed/34696226
http://dx.doi.org/10.3390/vaccines9101118
work_keys_str_mv AT wangzhiwei identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT ranling identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT chenchunxia identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT shiranran identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT dongyu identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT liyubing identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT zhouxiuman identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT qiyuanming identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT zhupingping identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT gaoyanfeng identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma
AT wuyahong identificationofhlaa2restrictedmutantepitopesfromneoantigensofesophagealsquamouscellcarcinoma