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T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer

Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure afte...

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Autores principales: Wu, Lirong, Zhu, Jun, Rudqvist, Nils-Petter, Welsh, James, Lee, Percy, Liao, Zhongxing, Xu, Ting, Jiang, Ming, Zhu, Xiangzhi, Pan, Xuan, Li, Pansong, Zhou, Zhipeng, He, Xia, Yin, Rong, Feng, Jifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559517/
https://www.ncbi.nlm.nih.gov/pubmed/34733273
http://dx.doi.org/10.3389/fimmu.2021.719285
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author Wu, Lirong
Zhu, Jun
Rudqvist, Nils-Petter
Welsh, James
Lee, Percy
Liao, Zhongxing
Xu, Ting
Jiang, Ming
Zhu, Xiangzhi
Pan, Xuan
Li, Pansong
Zhou, Zhipeng
He, Xia
Yin, Rong
Feng, Jifeng
author_facet Wu, Lirong
Zhu, Jun
Rudqvist, Nils-Petter
Welsh, James
Lee, Percy
Liao, Zhongxing
Xu, Ting
Jiang, Ming
Zhu, Xiangzhi
Pan, Xuan
Li, Pansong
Zhou, Zhipeng
He, Xia
Yin, Rong
Feng, Jifeng
author_sort Wu, Lirong
collection PubMed
description Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P<0.001). Frequencies in V/J gene fragment expression in the TCR β chain were also different for patients with or without metastases (two V fragments in baseline samples and 2 J and 9 V fragments in post-treatment samples). This comprehensive analysis of immune status before and after SBRT showed that quantitative assessments of TCRs can help evaluate prognosis in early-stage NSCLC.
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spelling pubmed-85595172021-11-02 T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer Wu, Lirong Zhu, Jun Rudqvist, Nils-Petter Welsh, James Lee, Percy Liao, Zhongxing Xu, Ting Jiang, Ming Zhu, Xiangzhi Pan, Xuan Li, Pansong Zhou, Zhipeng He, Xia Yin, Rong Feng, Jifeng Front Immunol Immunology Radiotherapy is known to influence immune function, including T cell receptor (TCR) repertoire. We evaluated the TCR repertoire before and after stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) and explored correlations between TCR indexes and distant failure after SBRT. TCR repertoires were analyzed in peripheral blood mononuclear cells (PBMCs) collected before and after SBRT from 19 patients. TCR combinational diversity in V and J genes was assessed with multiplex PCR of genomic DNA from PBMCs and tested for associations with clinical response. All patients received definitive SBRT to a biologically effective dose of >=100 Gy. The number of unique TCR clones was decreased after SBRT versus before, but clonality and the Shannon Entropy did not change. Four patients (21%) developed distant metastases after SBRT (median 7 months); those patients had lower Shannon Entropy in post-SBRT samples than patients without metastasis. Patients with a low change in Shannon Entropy from before to after SBRT [(post-SBRT Shannon Entropy minus baseline Shannon)/(baseline Shannon) * 100] had poorer metastasis-free survival than those with high change in Shannon Entropy (P<0.001). Frequencies in V/J gene fragment expression in the TCR β chain were also different for patients with or without metastases (two V fragments in baseline samples and 2 J and 9 V fragments in post-treatment samples). This comprehensive analysis of immune status before and after SBRT showed that quantitative assessments of TCRs can help evaluate prognosis in early-stage NSCLC. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8559517/ /pubmed/34733273 http://dx.doi.org/10.3389/fimmu.2021.719285 Text en Copyright © 2021 Wu, Zhu, Rudqvist, Welsh, Lee, Liao, Xu, Jiang, Zhu, Pan, Li, Zhou, He, Yin and Feng 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
Wu, Lirong
Zhu, Jun
Rudqvist, Nils-Petter
Welsh, James
Lee, Percy
Liao, Zhongxing
Xu, Ting
Jiang, Ming
Zhu, Xiangzhi
Pan, Xuan
Li, Pansong
Zhou, Zhipeng
He, Xia
Yin, Rong
Feng, Jifeng
T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
title T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
title_full T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
title_fullStr T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
title_full_unstemmed T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
title_short T-Cell Receptor Profiling and Prognosis After Stereotactic Body Radiation Therapy For Stage I Non-Small-Cell Lung Cancer
title_sort t-cell receptor profiling and prognosis after stereotactic body radiation therapy for stage i non-small-cell lung cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559517/
https://www.ncbi.nlm.nih.gov/pubmed/34733273
http://dx.doi.org/10.3389/fimmu.2021.719285
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