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Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression

INTRODUCTION: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. METHODS: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune rec...

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Autores principales: Pakasticali, Nagehan, Chobrutskiy, Andrea, Patel, Dhruv N., Hsiang, Monica, Zaman, Saif, Cios, Konrad J., Blanck, George, Chobrutskiy, Boris I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259117/
https://www.ncbi.nlm.nih.gov/pubmed/37313373
http://dx.doi.org/10.1177/11769351231177269
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author Pakasticali, Nagehan
Chobrutskiy, Andrea
Patel, Dhruv N.
Hsiang, Monica
Zaman, Saif
Cios, Konrad J.
Blanck, George
Chobrutskiy, Boris I.
author_facet Pakasticali, Nagehan
Chobrutskiy, Andrea
Patel, Dhruv N.
Hsiang, Monica
Zaman, Saif
Cios, Konrad J.
Blanck, George
Chobrutskiy, Boris I.
author_sort Pakasticali, Nagehan
collection PubMed
description INTRODUCTION: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. METHODS: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data. RESULTS: We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s. Also, we have established gene expression correlations with the high TCR CDR3-CTA chemical complementarities, for Granzyme B, and other immune biomarkers. CONCLUSIONS: Overall, for several independent TCR CDR3 breast cancer datasets, the CTA, ARMC3, stood out as a completely novel, candidate antigen based on multiple algorithms with highly consistent approaches. This conclusion was facilitated by use of the recently constructed Adaptive Match web tool.
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spelling pubmed-102591172023-06-13 Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression Pakasticali, Nagehan Chobrutskiy, Andrea Patel, Dhruv N. Hsiang, Monica Zaman, Saif Cios, Konrad J. Blanck, George Chobrutskiy, Boris I. Cancer Inform Original Research INTRODUCTION: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. METHODS: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data. RESULTS: We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s. Also, we have established gene expression correlations with the high TCR CDR3-CTA chemical complementarities, for Granzyme B, and other immune biomarkers. CONCLUSIONS: Overall, for several independent TCR CDR3 breast cancer datasets, the CTA, ARMC3, stood out as a completely novel, candidate antigen based on multiple algorithms with highly consistent approaches. This conclusion was facilitated by use of the recently constructed Adaptive Match web tool. SAGE Publications 2023-06-01 /pmc/articles/PMC10259117/ /pubmed/37313373 http://dx.doi.org/10.1177/11769351231177269 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Pakasticali, Nagehan
Chobrutskiy, Andrea
Patel, Dhruv N.
Hsiang, Monica
Zaman, Saif
Cios, Konrad J.
Blanck, George
Chobrutskiy, Boris I.
Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
title Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
title_full Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
title_fullStr Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
title_full_unstemmed Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
title_short Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
title_sort chemical complementarity of breast cancer resident, t-cell receptor cdr3 domains and the cancer antigen, armc3, is associated with higher levels of survival and granzyme expression
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10259117/
https://www.ncbi.nlm.nih.gov/pubmed/37313373
http://dx.doi.org/10.1177/11769351231177269
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