PMID- 32420064
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220414
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 9
IP  - 2
DP  - 2020 Apr
TI  - Heterogeneity of neoantigen landscape between primary lesions and their matched 
      metastases in lung cancer.
PG  - 246-256
LID - 10.21037/tlcr.2020.03.03 [doi]
AB  - BACKGROUND: Personalized cancer vaccines based on tumor-derived neoantigens have 
      shown strong and long-lasting antitumor effect in patients with some solid 
      tumors. However, whether neoantigens identified from primary lesions could 
      represent their metastatic lesions, and consequently the effect of vaccine 
      therapy remained unknown. METHODS: To investigate whether neoantigens identified 
      from primary tumors are similar to their matched metastases in lung cancer, we 
      identified 79 samples from 24 cases. All of samples were collected before any 
      systemic therapy. Major criteria for neoantigen identification included: derived 
      from tumor-specific mutations, fold change >10 comparing to germline expression 
      level, high predicted human leukocyte antigen (HLA) binding affinity and peptide 
      of 9-11 amino acids in length. RESULTS: We found a wide range of tumor neoantigen 
      burden in both primaries and metastases. The counts, overall distribution pattern 
      and predicted HLA binding affinity of neoantigens were similar between primaries 
      and metastases. However, only 20% of shared neoantigens (presented in both 
      primaries and metastases) was observed, which were mainly derived from single 
      nucleotide variants (SNVs) and fusions. A variety of corresponding HLA alleles 
      were observed and 50.0% of cases were HLA-C*06:02. Finally, we observed the 
      neoantigen intrametastases homogeneity in patients with sole brain metastases. 
      CONCLUSIONS: Neoantigen landscape in terms of the number, type and predicted HLA 
      binding affinity was similar between primaries and metastases, but the percentage 
      of shared neoantigens is only modest, suggesting vaccine development based solely 
      on primary tumor neoantigen may not offer optimal therapeutic outcome, and shared 
      neoantigen needs to be seriously considered.
CI  - 2020 Translational Lung Cancer Research. All rights reserved.
FAU - Jiang, Tao
AU  - Jiang T
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai 200433, China.
FAU - Cheng, Ruirui
AU  - Cheng R
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou 450052, China.
FAU - Pan, Yuanwei
AU  - Pan Y
AD  - Department of Imaging and Nuclear Medicine, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou 450052, China.
FAU - Zhang, Henghui
AU  - Zhang H
AD  - Beijing Genecast Biotechnology Co., Beijing 100000, China.
FAU - He, Ying
AU  - He Y
AD  - Shanghai Hengrui Pharmaceutical Co., LTD, Shanghai 200245, China.
FAU - Su, Chunxia
AU  - Su C
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai 200433, China.
FAU - Ren, Shengxiang
AU  - Ren S
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai 200433, China.
FAU - Zhou, Caicun
AU  - Zhou C
AD  - Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer 
      Institute, Tongji University School of Medicine, Shanghai 200433, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC7225166
OTO - NOTNLM
OT  - Lung cancer
OT  - metastasis
OT  - neoantigen
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/tlcr.2020.03.03). CZ serves as an 
      unpaid Editor-in-Chief of Translational Lung Cancer Research. The other authors 
      have no conflicts of interest to declare.
EDAT- 2020/05/19 06:00
MHDA- 2020/05/19 06:01
PMCR- 2020/04/01
CRDT- 2020/05/19 06:00
PHST- 2020/05/19 06:00 [entrez]
PHST- 2020/05/19 06:00 [pubmed]
PHST- 2020/05/19 06:01 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - tlcr-09-02-246 [pii]
AID - 10.21037/tlcr.2020.03.03 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2020 Apr;9(2):246-256. doi: 10.21037/tlcr.2020.03.03.