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PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression
Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potent...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094894/ https://www.ncbi.nlm.nih.gov/pubmed/37047395 http://dx.doi.org/10.3390/ijms24076420 |
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author | Alkaabi, Duaa Arafat, Kholoud Sulaiman, Shahrazad Al-Azawi, Aya Mudhafar Attoub, Samir |
author_facet | Alkaabi, Duaa Arafat, Kholoud Sulaiman, Shahrazad Al-Azawi, Aya Mudhafar Attoub, Samir |
author_sort | Alkaabi, Duaa |
collection | PubMed |
description | Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively. |
format | Online Article Text |
id | pubmed-10094894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100948942023-04-13 PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression Alkaabi, Duaa Arafat, Kholoud Sulaiman, Shahrazad Al-Azawi, Aya Mudhafar Attoub, Samir Int J Mol Sci Article Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively. MDPI 2023-03-29 /pmc/articles/PMC10094894/ /pubmed/37047395 http://dx.doi.org/10.3390/ijms24076420 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alkaabi, Duaa Arafat, Kholoud Sulaiman, Shahrazad Al-Azawi, Aya Mudhafar Attoub, Samir PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression |
title | PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression |
title_full | PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression |
title_fullStr | PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression |
title_full_unstemmed | PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression |
title_short | PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression |
title_sort | pd-1 independent role of pd-l1 in triple-negative breast cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094894/ https://www.ncbi.nlm.nih.gov/pubmed/37047395 http://dx.doi.org/10.3390/ijms24076420 |
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