MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design
Abstract Background Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for th...
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doaj-f6bfdb2d5f2940db93d6e47302b7ff302020-11-25T01:24:45ZengBMCBMC Genomics1471-21642018-08-011911910.1186/s12864-018-4958-5MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine designWeijing Cai0Dapeng Zhou1Weibo Wu2Wen Ling Tan3Jiaqian Wang4Caicun Zhou5Yanyan Lou6Shanghai Pulmonary Hospital affiliated with Tongji University School of MedicineShanghai Pulmonary Hospital affiliated with Tongji University School of MedicineShanghai Pulmonary Hospital affiliated with Tongji University School of MedicineShanghai Pulmonary Hospital affiliated with Tongji University School of MedicineYuceBio Technology Co., LtdShanghai Pulmonary Hospital affiliated with Tongji University School of MedicineDivision of Hematology and Oncology, Mayo ClinicAbstract Background Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for the efficacy of immune checkpoint blockade therapy by PD1 antibody. Results In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules. We found 18,175 expressed clonal somatic mutations, with an average of 124 per patient. The presentation of mutant peptides by an HLA(human leukocyte antigen) Class II molecule, HLA DRB1, were predicted by NetMHCIIpan3.1. 8804 neo-peptides, including 375 strong binders and 8429 weak binders were found. For HLA DRB1*01:01, 54 strong binders and 896 weak binders were found. The most commonly mutated genes with predicted neo-antigens are KRAS, TTN, RYR2, MUC16, TP53, USH2A, ZFHX4, KEAP1, STK11, FAT3, NAV3 and EGFR. Conclusions Our results support the feasibility of discovering individualized HLA Class II presented mutant peptides as candidates for immunodiagnosis and immunotherapy of lung adenocarcinoma.http://link.springer.com/article/10.1186/s12864-018-4958-5Lung cancerNeo-antigenCancer vaccinePD1 checkpoint blocking antibody |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weijing Cai Dapeng Zhou Weibo Wu Wen Ling Tan Jiaqian Wang Caicun Zhou Yanyan Lou |
spellingShingle |
Weijing Cai Dapeng Zhou Weibo Wu Wen Ling Tan Jiaqian Wang Caicun Zhou Yanyan Lou MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design BMC Genomics Lung cancer Neo-antigen Cancer vaccine PD1 checkpoint blocking antibody |
author_facet |
Weijing Cai Dapeng Zhou Weibo Wu Wen Ling Tan Jiaqian Wang Caicun Zhou Yanyan Lou |
author_sort |
Weijing Cai |
title |
MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design |
title_short |
MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design |
title_full |
MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design |
title_fullStr |
MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design |
title_full_unstemmed |
MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design |
title_sort |
mhc class ii restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2018-08-01 |
description |
Abstract Background Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for the efficacy of immune checkpoint blockade therapy by PD1 antibody. Results In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules. We found 18,175 expressed clonal somatic mutations, with an average of 124 per patient. The presentation of mutant peptides by an HLA(human leukocyte antigen) Class II molecule, HLA DRB1, were predicted by NetMHCIIpan3.1. 8804 neo-peptides, including 375 strong binders and 8429 weak binders were found. For HLA DRB1*01:01, 54 strong binders and 896 weak binders were found. The most commonly mutated genes with predicted neo-antigens are KRAS, TTN, RYR2, MUC16, TP53, USH2A, ZFHX4, KEAP1, STK11, FAT3, NAV3 and EGFR. Conclusions Our results support the feasibility of discovering individualized HLA Class II presented mutant peptides as candidates for immunodiagnosis and immunotherapy of lung adenocarcinoma. |
topic |
Lung cancer Neo-antigen Cancer vaccine PD1 checkpoint blocking antibody |
url |
http://link.springer.com/article/10.1186/s12864-018-4958-5 |
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