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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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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. |
format | Online Article Text |
id | pubmed-7225166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
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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