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High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy

Cancer genome instability leads to accumulation of mutations which may result into tumor-specific mutated “neoantigens”, not be affected by central T-cell tolerance. Such neoantigens are considered the optimal target for the patient’s anti-tumor T cell immunity as well as for personalized cancer imm...

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Autores principales: Mauriello, Angela, Zeuli, Roberta, Cavalluzzo, Beatrice, Petrizzo, Annacarmen, Tornesello, Maria Lina, Buonaguro, Franco M., Ceccarelli, Michele, Tagliamonte, Maria, Buonaguro, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966682/
https://www.ncbi.nlm.nih.gov/pubmed/31756926
http://dx.doi.org/10.3390/cancers11121824
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author Mauriello, Angela
Zeuli, Roberta
Cavalluzzo, Beatrice
Petrizzo, Annacarmen
Tornesello, Maria Lina
Buonaguro, Franco M.
Ceccarelli, Michele
Tagliamonte, Maria
Buonaguro, Luigi
author_facet Mauriello, Angela
Zeuli, Roberta
Cavalluzzo, Beatrice
Petrizzo, Annacarmen
Tornesello, Maria Lina
Buonaguro, Franco M.
Ceccarelli, Michele
Tagliamonte, Maria
Buonaguro, Luigi
author_sort Mauriello, Angela
collection PubMed
description Cancer genome instability leads to accumulation of mutations which may result into tumor-specific mutated “neoantigens”, not be affected by central T-cell tolerance. Such neoantigens are considered the optimal target for the patient’s anti-tumor T cell immunity as well as for personalized cancer immunotherapy strategies. However, only a minor fraction of predicted neoantigens are relevant to the clinical outcome. In the present study, a prediction algorithm was applied using datasets of RNA sequencing from all 377 Hepatocellular carcinoma (HCC) patients available at The Cancer Genome Atlas (TCGA), to predict neoantigens to be presented by each patient’s autologous HLA molecules. Correlation with patients’ survival was performed on the 115 samples for whom the exact date of death was known. A total of 30 samples were used for the training set, and 85 samples were used for the validation sets. Neither the somatic mutations nor the number nor the quality of the predicted neoantigens correlate as single parameter with survival of HCC patients who do not undergo immunotherapy treatment. Furthermore, the preferential presentation of such neoantigens in the context of one of the major histocompatibility complex MHC class I molecules does not have an impact on the survival. On the contrary, the expression of Granzyme A (GZMA) is significantly correlated with survival and, in the context of high GZMA, a direct correlation between number and quality of neoantigens with survival is observed. This is in striking contrast to results described in cancer patients undergoing immunotherapy, in which a strong correlation between Tumor Mutational Burden (TMB), number of predicted neoantigens and survival has been reported.
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spelling pubmed-69666822020-02-04 High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy Mauriello, Angela Zeuli, Roberta Cavalluzzo, Beatrice Petrizzo, Annacarmen Tornesello, Maria Lina Buonaguro, Franco M. Ceccarelli, Michele Tagliamonte, Maria Buonaguro, Luigi Cancers (Basel) Article Cancer genome instability leads to accumulation of mutations which may result into tumor-specific mutated “neoantigens”, not be affected by central T-cell tolerance. Such neoantigens are considered the optimal target for the patient’s anti-tumor T cell immunity as well as for personalized cancer immunotherapy strategies. However, only a minor fraction of predicted neoantigens are relevant to the clinical outcome. In the present study, a prediction algorithm was applied using datasets of RNA sequencing from all 377 Hepatocellular carcinoma (HCC) patients available at The Cancer Genome Atlas (TCGA), to predict neoantigens to be presented by each patient’s autologous HLA molecules. Correlation with patients’ survival was performed on the 115 samples for whom the exact date of death was known. A total of 30 samples were used for the training set, and 85 samples were used for the validation sets. Neither the somatic mutations nor the number nor the quality of the predicted neoantigens correlate as single parameter with survival of HCC patients who do not undergo immunotherapy treatment. Furthermore, the preferential presentation of such neoantigens in the context of one of the major histocompatibility complex MHC class I molecules does not have an impact on the survival. On the contrary, the expression of Granzyme A (GZMA) is significantly correlated with survival and, in the context of high GZMA, a direct correlation between number and quality of neoantigens with survival is observed. This is in striking contrast to results described in cancer patients undergoing immunotherapy, in which a strong correlation between Tumor Mutational Burden (TMB), number of predicted neoantigens and survival has been reported. MDPI 2019-11-20 /pmc/articles/PMC6966682/ /pubmed/31756926 http://dx.doi.org/10.3390/cancers11121824 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mauriello, Angela
Zeuli, Roberta
Cavalluzzo, Beatrice
Petrizzo, Annacarmen
Tornesello, Maria Lina
Buonaguro, Franco M.
Ceccarelli, Michele
Tagliamonte, Maria
Buonaguro, Luigi
High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy
title High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy
title_full High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy
title_fullStr High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy
title_full_unstemmed High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy
title_short High Somatic Mutation and Neoantigen Burden Do Not Correlate with Decreased Progression-Free Survival in HCC Patients not Undergoing Immunotherapy
title_sort high somatic mutation and neoantigen burden do not correlate with decreased progression-free survival in hcc patients not undergoing immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966682/
https://www.ncbi.nlm.nih.gov/pubmed/31756926
http://dx.doi.org/10.3390/cancers11121824
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