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TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types

Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. W...

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Autores principales: Cao, Jia-Zheng, Yao, Gao-Sheng, Liu, Fei, Tang, Yi-Ming, Li, Peng-Ju, Feng, Zi-Hao, Luo, Jun-Hang, Wei, Jin-Huan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004558/
https://www.ncbi.nlm.nih.gov/pubmed/35344507
http://dx.doi.org/10.18632/aging.203980
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author Cao, Jia-Zheng
Yao, Gao-Sheng
Liu, Fei
Tang, Yi-Ming
Li, Peng-Ju
Feng, Zi-Hao
Luo, Jun-Hang
Wei, Jin-Huan
author_facet Cao, Jia-Zheng
Yao, Gao-Sheng
Liu, Fei
Tang, Yi-Ming
Li, Peng-Ju
Feng, Zi-Hao
Luo, Jun-Hang
Wei, Jin-Huan
author_sort Cao, Jia-Zheng
collection PubMed
description Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. We downloaded somatic mutation data for 46,697 patients and tumor-infiltrating immune cells levels data for 11070 patients, then combined TP53 and BRAF mutation status into a biomarker model and found that the predict ability of TP53/BRAF mutation model is more powerful than some past models. Commonly, patients with high-TMB status have better response to ICI therapy than patients with low-TMB status. However, the genotype of TP53(MUT)BRAF(WT) in high-TMB status cohort have poorer response to ICI therapy than the genotype of BRAF(MUT)TP53(WT) in low-TMB status (Median, 18 months vs 47 month). Thus, TP53/BRAF mutation model can add predictive value to TMB in identifying patients who benefited from ICI treatment, which can enable more informed treatment decisions.
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spelling pubmed-90045582022-04-13 TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types Cao, Jia-Zheng Yao, Gao-Sheng Liu, Fei Tang, Yi-Ming Li, Peng-Ju Feng, Zi-Hao Luo, Jun-Hang Wei, Jin-Huan Aging (Albany NY) Research Paper Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. We downloaded somatic mutation data for 46,697 patients and tumor-infiltrating immune cells levels data for 11070 patients, then combined TP53 and BRAF mutation status into a biomarker model and found that the predict ability of TP53/BRAF mutation model is more powerful than some past models. Commonly, patients with high-TMB status have better response to ICI therapy than patients with low-TMB status. However, the genotype of TP53(MUT)BRAF(WT) in high-TMB status cohort have poorer response to ICI therapy than the genotype of BRAF(MUT)TP53(WT) in low-TMB status (Median, 18 months vs 47 month). Thus, TP53/BRAF mutation model can add predictive value to TMB in identifying patients who benefited from ICI treatment, which can enable more informed treatment decisions. Impact Journals 2022-03-27 /pmc/articles/PMC9004558/ /pubmed/35344507 http://dx.doi.org/10.18632/aging.203980 Text en Copyright: © 2022 Cao et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cao, Jia-Zheng
Yao, Gao-Sheng
Liu, Fei
Tang, Yi-Ming
Li, Peng-Ju
Feng, Zi-Hao
Luo, Jun-Hang
Wei, Jin-Huan
TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
title TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
title_full TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
title_fullStr TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
title_full_unstemmed TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
title_short TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
title_sort tp53/braf mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004558/
https://www.ncbi.nlm.nih.gov/pubmed/35344507
http://dx.doi.org/10.18632/aging.203980
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