PMID- 30075702
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 19
IP  - 1
DP  - 2018 Aug 3
TI  - MHC class II restricted neoantigen peptides predicted by clonal mutation analysis 
      in lung adenocarcinoma patients: implications on prognostic immunological 
      biomarker and vaccine design.
PG  - 582
LID - 10.1186/s12864-018-4958-5 [doi]
LID - 582
AB  - 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.
FAU - Cai, Weijing
AU  - Cai W
AD  - Shanghai Pulmonary Hospital affiliated with Tongji University School of Medicine, 
      Shanghai, 200092, China.
FAU - Zhou, Dapeng
AU  - Zhou D
AUID- ORCID: 0000-0003-1347-3811
AD  - Shanghai Pulmonary Hospital affiliated with Tongji University School of Medicine, 
      Shanghai, 200092, China. dapengzhoulab@tongji.edu.cn.
FAU - Wu, Weibo
AU  - Wu W
AD  - Shanghai Pulmonary Hospital affiliated with Tongji University School of Medicine, 
      Shanghai, 200092, China.
FAU - Tan, Wen Ling
AU  - Tan WL
AD  - Shanghai Pulmonary Hospital affiliated with Tongji University School of Medicine, 
      Shanghai, 200092, China.
FAU - Wang, Jiaqian
AU  - Wang J
AD  - YuceBio Technology Co., Ltd, Shanghai, 201203, China.
FAU - Zhou, Caicun
AU  - Zhou C
AD  - Shanghai Pulmonary Hospital affiliated with Tongji University School of Medicine, 
      Shanghai, 200092, China.
FAU - Lou, Yanyan
AU  - Lou Y
AD  - Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, 32224, USA. 
      Lou.Yanyan@mayo.edu.
LA  - eng
GR  - 81570007/National Natural Science Foundation of China grant/
PT  - Journal Article
DEP - 20180803
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Peptides)
SB  - IM
MH  - Adenocarcinoma of Lung/*genetics/immunology
MH  - Antigens, Neoplasm/immunology
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - DNA Mutational Analysis/*methods
MH  - Databases, Genetic
MH  - HLA-DRB1 Chains/*immunology
MH  - High-Throughput Nucleotide Sequencing/methods
MH  - Humans
MH  - Immunologic Tests
MH  - Immunotherapy
MH  - Peptides/*genetics/metabolism
MH  - Sequence Analysis, DNA/methods
PMC - PMC6090856
OTO - NOTNLM
OT  - Cancer vaccine
OT  - Lung cancer
OT  - Neo-antigen
OT  - PD1 checkpoint blocking antibody
COIS- Not applicable. Not applicable. The authors declare that they have no competing 
      interests. Springer Nature remains neutral with regard to jurisdictional claims 
      in published maps and institutional affiliations.
EDAT- 2018/08/05 06:00
MHDA- 2018/12/12 06:00
PMCR- 2018/08/03
CRDT- 2018/08/05 06:00
PHST- 2017/08/22 00:00 [received]
PHST- 2018/07/24 00:00 [accepted]
PHST- 2018/08/05 06:00 [entrez]
PHST- 2018/08/05 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/08/03 00:00 [pmc-release]
AID - 10.1186/s12864-018-4958-5 [pii]
AID - 4958 [pii]
AID - 10.1186/s12864-018-4958-5 [doi]
PST - epublish
SO  - BMC Genomics. 2018 Aug 3;19(1):582. doi: 10.1186/s12864-018-4958-5.