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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...

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Autores principales: Gan, Fanyi, Zhang, Chuanfen, Xia, Liang, Deng, Senyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
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.
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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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