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Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (...

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Autores principales: Sun, Jing, Bai, Hua, Wang, Zhijie, Duan, Jianchun, Li, Jin, Guo, Ruimin, Wang, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049512/
https://www.ncbi.nlm.nih.gov/pubmed/32020764
http://dx.doi.org/10.1111/1759-7714.13322
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author Sun, Jing
Bai, Hua
Wang, Zhijie
Duan, Jianchun
Li, Jin
Guo, Ruimin
Wang, Jie
author_facet Sun, Jing
Bai, Hua
Wang, Zhijie
Duan, Jianchun
Li, Jin
Guo, Ruimin
Wang, Jie
author_sort Sun, Jing
collection PubMed
description BACKGROUND: Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG‐rhG‐CSF influences immune cells, such as lymphocytes, remains unclear. METHODS: A total of 17 treatment‐naïve SCLC patients were prospectively enrolled and divided into the PEG‐rhG‐CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4–6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3(+) T, CD4(+) T, CD8(+) T, NK, and B cells. The diversity and clonality of the T‐cell receptor (TCR) repertoire was analyzed by next‐generation sequencing. RESULTS: In the PEG‐rhG‐CSF group, the proportions of CD3(+) T and CD4(+) T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8(+) T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG‐rhG‐CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vβ and Jβ gene fragment types, which determine TCR diversity, were significantly amplified in the PEG‐rhG‐CSF group. The change in TCR diversity was significantly correlated with changes in the CD3(+) T or CD4(+) T cell proportions, but not the CD8(+) T cell proportion. CONCLUSIONS: PEG‐rhG‐CSF regulates the immune status of SCLC patients; CD4(+) T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC. KEY POINTS: PEG‐rhG‐CSF regulates SCLC immunity. PEG‐rhG‐CSF increased CD3(+) T and CD4(+)T cell proportions. PEG‐rhG‐CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3(+) T or CD4(+) T changes.
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spelling pubmed-70495122020-03-05 Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer Sun, Jing Bai, Hua Wang, Zhijie Duan, Jianchun Li, Jin Guo, Ruimin Wang, Jie Thorac Cancer Original Articles BACKGROUND: Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG‐rhG‐CSF influences immune cells, such as lymphocytes, remains unclear. METHODS: A total of 17 treatment‐naïve SCLC patients were prospectively enrolled and divided into the PEG‐rhG‐CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4–6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3(+) T, CD4(+) T, CD8(+) T, NK, and B cells. The diversity and clonality of the T‐cell receptor (TCR) repertoire was analyzed by next‐generation sequencing. RESULTS: In the PEG‐rhG‐CSF group, the proportions of CD3(+) T and CD4(+) T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8(+) T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG‐rhG‐CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vβ and Jβ gene fragment types, which determine TCR diversity, were significantly amplified in the PEG‐rhG‐CSF group. The change in TCR diversity was significantly correlated with changes in the CD3(+) T or CD4(+) T cell proportions, but not the CD8(+) T cell proportion. CONCLUSIONS: PEG‐rhG‐CSF regulates the immune status of SCLC patients; CD4(+) T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC. KEY POINTS: PEG‐rhG‐CSF regulates SCLC immunity. PEG‐rhG‐CSF increased CD3(+) T and CD4(+)T cell proportions. PEG‐rhG‐CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3(+) T or CD4(+) T changes. John Wiley & Sons Australia, Ltd 2020-02-05 2020-03 /pmc/articles/PMC7049512/ /pubmed/32020764 http://dx.doi.org/10.1111/1759-7714.13322 Text en © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Sun, Jing
Bai, Hua
Wang, Zhijie
Duan, Jianchun
Li, Jin
Guo, Ruimin
Wang, Jie
Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
title Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
title_full Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
title_fullStr Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
title_full_unstemmed Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
title_short Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
title_sort pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049512/
https://www.ncbi.nlm.nih.gov/pubmed/32020764
http://dx.doi.org/10.1111/1759-7714.13322
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