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Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis

BACKGROUND: Immunotherapy has had a high success rate in treating lung adenocarcinoma (LUAD) for several decades. However, many patients do not benefit from immunotherapy alone. Recent studies revealed that a combination of immunotherapy and radiotherapy (RT) stimulates a good systemic immune respon...

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Autores principales: Sun, Lu, Zhou, Haiting, Wu, Cheng, Peng, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643968/
https://www.ncbi.nlm.nih.gov/pubmed/37969379
http://dx.doi.org/10.21037/tcr-23-968
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author Sun, Lu
Zhou, Haiting
Wu, Cheng
Peng, Yi
author_facet Sun, Lu
Zhou, Haiting
Wu, Cheng
Peng, Yi
author_sort Sun, Lu
collection PubMed
description BACKGROUND: Immunotherapy has had a high success rate in treating lung adenocarcinoma (LUAD) for several decades. However, many patients do not benefit from immunotherapy alone. Recent studies revealed that a combination of immunotherapy and radiotherapy (RT) stimulates a good systemic immune response to LUAD. However, clinical and experimental evidence suggest that RT may give rise to primary immunodeficiency, facilitating tumor immunity escape. Little is known about the molecular mechanisms whereby RT and stereotactic body radiotherapy (SBRT) influence tumor immunogenicity and the effectiveness of immunotherapy in patients with LUAD. METHODS: We investigated molecular markers that predict response to combination of immunotherapy and SBRT in the treatment of LUAD using bioinformatics. RESULTS: SBRT significantly upregulated the expression of PTPRC, LILRB2, TLR8, CCR5, and PLEK and significantly downregulated the expression of CXCL13, CD19, and LTA. Among these genes, the expression of PTPRC, TLR8, and CCR5 was associated with responsiveness to immunotherapy after SBRT. However, only TLR8 and CCR5 expression were associated with an improved prognosis. Further analysis revealed that TLR8 and CCR5 expression increased responsiveness to immunotherapy by promoting M0 macrophage and memory B cell infiltration of LUAD tissues. CONCLUSIONS: In patients with LUAD, TLR8 and CCR5 expression are potential markers of a favorable response to combined immunotherapy and RT.
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spelling pubmed-106439682023-11-15 Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis Sun, Lu Zhou, Haiting Wu, Cheng Peng, Yi Transl Cancer Res Original Article BACKGROUND: Immunotherapy has had a high success rate in treating lung adenocarcinoma (LUAD) for several decades. However, many patients do not benefit from immunotherapy alone. Recent studies revealed that a combination of immunotherapy and radiotherapy (RT) stimulates a good systemic immune response to LUAD. However, clinical and experimental evidence suggest that RT may give rise to primary immunodeficiency, facilitating tumor immunity escape. Little is known about the molecular mechanisms whereby RT and stereotactic body radiotherapy (SBRT) influence tumor immunogenicity and the effectiveness of immunotherapy in patients with LUAD. METHODS: We investigated molecular markers that predict response to combination of immunotherapy and SBRT in the treatment of LUAD using bioinformatics. RESULTS: SBRT significantly upregulated the expression of PTPRC, LILRB2, TLR8, CCR5, and PLEK and significantly downregulated the expression of CXCL13, CD19, and LTA. Among these genes, the expression of PTPRC, TLR8, and CCR5 was associated with responsiveness to immunotherapy after SBRT. However, only TLR8 and CCR5 expression were associated with an improved prognosis. Further analysis revealed that TLR8 and CCR5 expression increased responsiveness to immunotherapy by promoting M0 macrophage and memory B cell infiltration of LUAD tissues. CONCLUSIONS: In patients with LUAD, TLR8 and CCR5 expression are potential markers of a favorable response to combined immunotherapy and RT. AME Publishing Company 2023-10-24 2023-10-31 /pmc/articles/PMC10643968/ /pubmed/37969379 http://dx.doi.org/10.21037/tcr-23-968 Text en 2023 Translational 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
Sun, Lu
Zhou, Haiting
Wu, Cheng
Peng, Yi
Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
title Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
title_full Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
title_fullStr Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
title_full_unstemmed Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
title_short Molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
title_sort molecular markers that predict response to combined radiotherapy and immunotherapy in patients with lung adenocarcinoma: a bioinformatics analysis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643968/
https://www.ncbi.nlm.nih.gov/pubmed/37969379
http://dx.doi.org/10.21037/tcr-23-968
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