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TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

Translational research on immune checkpoint inhibitors (ICIs) has been underway. However, in the unselected population, only a few patients benefit from ICIs. Therefore, screening predictive markers of ICI efficacy has become the current focus of attention. We collected mutation and clinical data fr...

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Autores principales: Lin, Anqi, Zhang, Hongman, Meng, Hui, Deng, Ze, Gu, Tianqi, Luo, Peng, Zhang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481577/
https://www.ncbi.nlm.nih.gov/pubmed/34603277
http://dx.doi.org/10.3389/fimmu.2021.667875
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author Lin, Anqi
Zhang, Hongman
Meng, Hui
Deng, Ze
Gu, Tianqi
Luo, Peng
Zhang, Jian
author_facet Lin, Anqi
Zhang, Hongman
Meng, Hui
Deng, Ze
Gu, Tianqi
Luo, Peng
Zhang, Jian
author_sort Lin, Anqi
collection PubMed
description Translational research on immune checkpoint inhibitors (ICIs) has been underway. However, in the unselected population, only a few patients benefit from ICIs. Therefore, screening predictive markers of ICI efficacy has become the current focus of attention. We collected mutation and clinical data from an ICI-treated non-small cell lung cancer (NSCLC) cohort. Then, a univariate Cox regression model was used to analyze the relationship between tumor necrosis factor α signaling mutated (TNFα-MT) and the prognosis of immunotherapy for NSCLC. We retrospectively collected 36 NSCLC patients (local-cohort) from the Zhujiang Hospital of Southern Medical University and performed whole-exome sequencing (WES). The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to explore the association between TNFα-MT and the immune microenvironment. A local cohort was used to validate the association between TNFα-MT and immunogenicity. TNFα-MT was associated with significantly prolonged overall survival (OS) in NSCLC patients after receiving immunotherapy. Additionally, TNFα-MT is related to high immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations) and enrichment of infiltrating immune cells. These results suggest that TNFα-MT may serve as a potential clinical biomarker for NSCLC patients receiving ICIs.
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spelling pubmed-84815772021-10-01 TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Lin, Anqi Zhang, Hongman Meng, Hui Deng, Ze Gu, Tianqi Luo, Peng Zhang, Jian Front Immunol Immunology Translational research on immune checkpoint inhibitors (ICIs) has been underway. However, in the unselected population, only a few patients benefit from ICIs. Therefore, screening predictive markers of ICI efficacy has become the current focus of attention. We collected mutation and clinical data from an ICI-treated non-small cell lung cancer (NSCLC) cohort. Then, a univariate Cox regression model was used to analyze the relationship between tumor necrosis factor α signaling mutated (TNFα-MT) and the prognosis of immunotherapy for NSCLC. We retrospectively collected 36 NSCLC patients (local-cohort) from the Zhujiang Hospital of Southern Medical University and performed whole-exome sequencing (WES). The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to explore the association between TNFα-MT and the immune microenvironment. A local cohort was used to validate the association between TNFα-MT and immunogenicity. TNFα-MT was associated with significantly prolonged overall survival (OS) in NSCLC patients after receiving immunotherapy. Additionally, TNFα-MT is related to high immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations) and enrichment of infiltrating immune cells. These results suggest that TNFα-MT may serve as a potential clinical biomarker for NSCLC patients receiving ICIs. Frontiers Media S.A. 2021-09-16 /pmc/articles/PMC8481577/ /pubmed/34603277 http://dx.doi.org/10.3389/fimmu.2021.667875 Text en Copyright © 2021 Lin, Zhang, Meng, Deng, Gu, Luo and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lin, Anqi
Zhang, Hongman
Meng, Hui
Deng, Ze
Gu, Tianqi
Luo, Peng
Zhang, Jian
TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
title TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
title_full TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
title_fullStr TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
title_full_unstemmed TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
title_short TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
title_sort tnf-alpha pathway alternation predicts survival of immune checkpoint inhibitors in non-small cell lung cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481577/
https://www.ncbi.nlm.nih.gov/pubmed/34603277
http://dx.doi.org/10.3389/fimmu.2021.667875
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