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Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer
BACKGROUND: Immunotherapy has emerged as a promising treatment strategy in malignant tumors. Inhibitors and neutralizing antibodies targeted PD-1 or PD-L1 show improved clinical outcomes in advanced non-small cell lung cancers (NSCLCs). Previous studies concluded that PD-1 was mainly expressed on ac...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841543/ https://www.ncbi.nlm.nih.gov/pubmed/35261880 http://dx.doi.org/10.21037/tcr-21-1644 |
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author | Gan, Fanyi Zhang, Chuanfen Xia, Liang Deng, Senyi |
author_facet | Gan, Fanyi Zhang, Chuanfen Xia, Liang Deng, Senyi |
author_sort | Gan, Fanyi |
collection | PubMed |
description | BACKGROUND: Immunotherapy has emerged as a promising treatment strategy in malignant tumors. Inhibitors and neutralizing antibodies targeted PD-1 or PD-L1 show improved clinical outcomes in advanced non-small cell lung cancers (NSCLCs). Previous studies concluded that PD-1 was mainly expressed on activated T cells, B cells and other immune cells. Recently, two studies suggested that PD-1 could be detected in the tumor cells of melanoma and hepatocellular carcinoma. Tumor-endogenous PD-1 in NSCLCs has not been reported at present. Thus, we intended to explore the expression and prognostic relevance of tumor-endogenous PD-1 in NSCLCs. METHODS: We detected the PD-1 expression in fresh tumor samples and tumor slices by flow cytometer and immunohistochemical analysis respectively. Overall survival (OS) and dis-ease-free survival (DFS) were analyzed with Kaplan-Meier survival curve. We explored the PD-1 expression in lung cancer cell lines and investigated its effect on cell proliferation. RESULTS: Flow cytometry showed that tumor cells with endogenous PD-1 constituted 2.08%, 2.42%, 1.79%, and 1.21% in 4 clinical NSCLC samples respectively. Thirty-four patients (34%) in the cohort were positive for tumor-endogenous PD-1 in IHC analysis. Patients with tumor-endogenous PD-1 had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified tumor-endogenous PD-1 as an independent risk factor (HR =3.807, 95% CI: 2.031–7.135, P<0.05). PD-1 could be observed in 4 kinds of lung cancer cell lines (A549, H1975, H1299 and HCC827). PD-1 overexpression could enhance proliferation and clone formation of these cell lines. CONCLUSIONS: PD-1 was endogenously expressed on the tumor cells of NSCLCs, and it could serve as an independent prognostic risk factor. The molecular mechanism of inferior survival of tumor-endogenous PD-1 may attribute to its role in promoting cell proliferation and clone formation. Our results demonstrated the non-immune role of PD-1 in tumor microenvironment and may provide new thinking for the therapy of NSCLCs. |
format | Online Article Text |
id | pubmed-8841543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-88415432022-03-07 Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer Gan, Fanyi Zhang, Chuanfen Xia, Liang Deng, Senyi Transl Cancer Res Original Article BACKGROUND: Immunotherapy has emerged as a promising treatment strategy in malignant tumors. Inhibitors and neutralizing antibodies targeted PD-1 or PD-L1 show improved clinical outcomes in advanced non-small cell lung cancers (NSCLCs). Previous studies concluded that PD-1 was mainly expressed on activated T cells, B cells and other immune cells. Recently, two studies suggested that PD-1 could be detected in the tumor cells of melanoma and hepatocellular carcinoma. Tumor-endogenous PD-1 in NSCLCs has not been reported at present. Thus, we intended to explore the expression and prognostic relevance of tumor-endogenous PD-1 in NSCLCs. METHODS: We detected the PD-1 expression in fresh tumor samples and tumor slices by flow cytometer and immunohistochemical analysis respectively. Overall survival (OS) and dis-ease-free survival (DFS) were analyzed with Kaplan-Meier survival curve. We explored the PD-1 expression in lung cancer cell lines and investigated its effect on cell proliferation. RESULTS: Flow cytometry showed that tumor cells with endogenous PD-1 constituted 2.08%, 2.42%, 1.79%, and 1.21% in 4 clinical NSCLC samples respectively. Thirty-four patients (34%) in the cohort were positive for tumor-endogenous PD-1 in IHC analysis. Patients with tumor-endogenous PD-1 had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified tumor-endogenous PD-1 as an independent risk factor (HR =3.807, 95% CI: 2.031–7.135, P<0.05). PD-1 could be observed in 4 kinds of lung cancer cell lines (A549, H1975, H1299 and HCC827). PD-1 overexpression could enhance proliferation and clone formation of these cell lines. CONCLUSIONS: PD-1 was endogenously expressed on the tumor cells of NSCLCs, and it could serve as an independent prognostic risk factor. The molecular mechanism of inferior survival of tumor-endogenous PD-1 may attribute to its role in promoting cell proliferation and clone formation. Our results demonstrated the non-immune role of PD-1 in tumor microenvironment and may provide new thinking for the therapy of NSCLCs. AME Publishing Company 2022-01 /pmc/articles/PMC8841543/ /pubmed/35261880 http://dx.doi.org/10.21037/tcr-21-1644 Text en 2022 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/. |
spellingShingle | Original Article Gan, Fanyi Zhang, Chuanfen Xia, Liang Deng, Senyi Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
title | Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
title_full | Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
title_fullStr | Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
title_full_unstemmed | Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
title_short | Tumor-endogenous PD-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
title_sort | tumor-endogenous pd-1 promotes cell proliferation and predicts poor survival in non-small cell lung cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841543/ https://www.ncbi.nlm.nih.gov/pubmed/35261880 http://dx.doi.org/10.21037/tcr-21-1644 |
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