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Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response

BACKGROUND: Further analysis of phase I trial of the KEYNOTE-001 has shown that previous radiotherapy improves the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab treatment, possibly explained by the radiation-induced specific anti-cancer immunity wit...

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Autores principales: Liu, Chao, Hu, Qinyong, Xu, Bin, Hu, Xiaoyu, Su, Huichao, Li, Qian, Zhang, Xiaoling, Yue, Jinbo, Yu, Jinming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505218/
https://www.ncbi.nlm.nih.gov/pubmed/31080362
http://dx.doi.org/10.1186/s12935-019-0839-5
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author Liu, Chao
Hu, Qinyong
Xu, Bin
Hu, Xiaoyu
Su, Huichao
Li, Qian
Zhang, Xiaoling
Yue, Jinbo
Yu, Jinming
author_facet Liu, Chao
Hu, Qinyong
Xu, Bin
Hu, Xiaoyu
Su, Huichao
Li, Qian
Zhang, Xiaoling
Yue, Jinbo
Yu, Jinming
author_sort Liu, Chao
collection PubMed
description BACKGROUND: Further analysis of phase I trial of the KEYNOTE-001 has shown that previous radiotherapy improves the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab treatment, possibly explained by the radiation-induced specific anti-cancer immunity with a memory effect. In this study, we aimed to investigate the peripheral memory and naïve T cells as predictors of early response in lung metastases post-stereotactic body radiotherapy (SBRT). METHODS: Sixty-six lung metastases patients with NSCLC who received SBRT were enrolled in this study. Analyses of peripheral memory CD4+ T, memory CD8+ T, naive CD4+ T, and naive CD8+ T in NSCLC patients were performed by flow cytometry. Evaluations of the link between immune cells and early radiation response a month after SBRT were carried out via logistic regression analyses. RESULTS: Higher levels of memory CD4+ T, memory CD8+ T, and lower levels of naïve CD4+ T, CD4+ naïve/memory ratio, and CD8+ naïve/memory ratio were shown in responders compared with non-responders (all P < 0.05). Logistic regression analyses of univariate and multivariate revealed that peripheral memory CD4+ T (OR: 0.14, 95% CI 0.04–0.50, P = 0.003; OR: 0.17, 95% CI 0.05–0.66, P = 0.010), memory CD8+ T (OR: 0.11, 95% CI 0.01–0.87, P = 0.037; OR: 0.11, 95% CI 0.01–0.97, P = 0.047), naïve CD4+ T (OR: 16.25, 95% CI 3.17–83.13, P = 0.001; OR: 12.67, 95% CI 2.26–71.18, P = 0.004) and CD4+ naïve/memory ratio (OR: 11.27, 95% CI 2.67–47.58, P = 0.001; OR: 8.50, 95% CI 1.90–38.14, P = 0.005) were independent predictors for tumor response to SBRT in the lung metastases of NSCLC patients. CONCLUSIONS: The tumor response of lung metastases a month after SBRT independently correlated with peripheral memory CD4+ T, memory CD8+ T, naïve CD4+ T, and CD4+ naïve/memory ratio. These findings could be helpful in incorporating additional treatments to improve clinical outcomes in the case of poor responders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0839-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-65052182019-05-10 Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response Liu, Chao Hu, Qinyong Xu, Bin Hu, Xiaoyu Su, Huichao Li, Qian Zhang, Xiaoling Yue, Jinbo Yu, Jinming Cancer Cell Int Primary Research BACKGROUND: Further analysis of phase I trial of the KEYNOTE-001 has shown that previous radiotherapy improves the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab treatment, possibly explained by the radiation-induced specific anti-cancer immunity with a memory effect. In this study, we aimed to investigate the peripheral memory and naïve T cells as predictors of early response in lung metastases post-stereotactic body radiotherapy (SBRT). METHODS: Sixty-six lung metastases patients with NSCLC who received SBRT were enrolled in this study. Analyses of peripheral memory CD4+ T, memory CD8+ T, naive CD4+ T, and naive CD8+ T in NSCLC patients were performed by flow cytometry. Evaluations of the link between immune cells and early radiation response a month after SBRT were carried out via logistic regression analyses. RESULTS: Higher levels of memory CD4+ T, memory CD8+ T, and lower levels of naïve CD4+ T, CD4+ naïve/memory ratio, and CD8+ naïve/memory ratio were shown in responders compared with non-responders (all P < 0.05). Logistic regression analyses of univariate and multivariate revealed that peripheral memory CD4+ T (OR: 0.14, 95% CI 0.04–0.50, P = 0.003; OR: 0.17, 95% CI 0.05–0.66, P = 0.010), memory CD8+ T (OR: 0.11, 95% CI 0.01–0.87, P = 0.037; OR: 0.11, 95% CI 0.01–0.97, P = 0.047), naïve CD4+ T (OR: 16.25, 95% CI 3.17–83.13, P = 0.001; OR: 12.67, 95% CI 2.26–71.18, P = 0.004) and CD4+ naïve/memory ratio (OR: 11.27, 95% CI 2.67–47.58, P = 0.001; OR: 8.50, 95% CI 1.90–38.14, P = 0.005) were independent predictors for tumor response to SBRT in the lung metastases of NSCLC patients. CONCLUSIONS: The tumor response of lung metastases a month after SBRT independently correlated with peripheral memory CD4+ T, memory CD8+ T, naïve CD4+ T, and CD4+ naïve/memory ratio. These findings could be helpful in incorporating additional treatments to improve clinical outcomes in the case of poor responders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0839-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-07 /pmc/articles/PMC6505218/ /pubmed/31080362 http://dx.doi.org/10.1186/s12935-019-0839-5 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Liu, Chao
Hu, Qinyong
Xu, Bin
Hu, Xiaoyu
Su, Huichao
Li, Qian
Zhang, Xiaoling
Yue, Jinbo
Yu, Jinming
Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
title Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
title_full Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
title_fullStr Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
title_full_unstemmed Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
title_short Peripheral memory and naïve T cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
title_sort peripheral memory and naïve t cells in non-small cell lung cancer patients with lung metastases undergoing stereotactic body radiotherapy: predictors of early tumor response
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505218/
https://www.ncbi.nlm.nih.gov/pubmed/31080362
http://dx.doi.org/10.1186/s12935-019-0839-5
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