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Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer

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 va...

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Autores principales: Jiang, Tao, Cheng, Ruirui, Pan, Yuanwei, Zhang, Henghui, He, Ying, Su, Chunxia, Ren, Shengxiang, Zhou, Caicun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225166/
https://www.ncbi.nlm.nih.gov/pubmed/32420064
http://dx.doi.org/10.21037/tlcr.2020.03.03
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author Jiang, Tao
Cheng, Ruirui
Pan, Yuanwei
Zhang, Henghui
He, Ying
Su, Chunxia
Ren, Shengxiang
Zhou, Caicun
author_facet Jiang, Tao
Cheng, Ruirui
Pan, Yuanwei
Zhang, Henghui
He, Ying
Su, Chunxia
Ren, Shengxiang
Zhou, Caicun
author_sort Jiang, Tao
collection PubMed
description 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.
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spelling pubmed-72251662020-05-15 Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer Jiang, Tao Cheng, Ruirui Pan, Yuanwei Zhang, Henghui He, Ying Su, Chunxia Ren, Shengxiang Zhou, Caicun Transl Lung Cancer Res Original Article 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. AME Publishing Company 2020-04 /pmc/articles/PMC7225166/ /pubmed/32420064 http://dx.doi.org/10.21037/tlcr.2020.03.03 Text en 2020 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Jiang, Tao
Cheng, Ruirui
Pan, Yuanwei
Zhang, Henghui
He, Ying
Su, Chunxia
Ren, Shengxiang
Zhou, Caicun
Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
title Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
title_full Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
title_fullStr Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
title_full_unstemmed Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
title_short Heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
title_sort heterogeneity of neoantigen landscape between primary lesions and their matched metastases in lung cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225166/
https://www.ncbi.nlm.nih.gov/pubmed/32420064
http://dx.doi.org/10.21037/tlcr.2020.03.03
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