PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib

BackgroundImmunotherapy plays a crucial role in the treatment of tumors. However, few studies have investigated the relationship between the expression of Programmed Cell Death Ligand 1 (PD-L1, CD274) in microvascular endothelial cells (MECs), including blood endothelial cells (BECs) and lymphatic e...

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Main Authors: Yingfang Feng, Yuan Gao, Shaochuan Liu, Tingting Qin, Yan Zhang, Jing Wang, Kai Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1544278/full
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author Yingfang Feng
Yuan Gao
Shaochuan Liu
Tingting Qin
Yan Zhang
Jing Wang
Kai Li
author_facet Yingfang Feng
Yuan Gao
Shaochuan Liu
Tingting Qin
Yan Zhang
Jing Wang
Kai Li
author_sort Yingfang Feng
collection DOAJ
description BackgroundImmunotherapy plays a crucial role in the treatment of tumors. However, few studies have investigated the relationship between the expression of Programmed Cell Death Ligand 1 (PD-L1, CD274) in microvascular endothelial cells (MECs), including blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and immune cell infiltration within tissues.MethodsIn our study, we utilized data from The Cancer Genome Atlas, a mouse subcutaneous xenograft model, and immunofluorescence and immunohistochemical staining to investigate the relationship between PD-L1 expression in melanoma MECs at different tumor stages and the infiltration of CD8+ T cells in tumor and normal organs, under conditions with and without anlotinib treatment.ResultsWe found that PD-L1 expression was upregulated in tumor MECs, while anlotinib downregulated PD-L1 expression in both tumor and normal tissue MECs, corresponding with increased infiltration of CD8+ T cells in the tissues. Additionally, the antitumor effect of anlotinib was most pronounced when administered during the mid-stage of tumor development.ConclusionsThis study evaluated the most effective timing for anlotinib to downregulate PD-L1 expression in tumor and normal tissues to promote immune infiltration. Our findings may offer valuable insights for the clinical use of anlotinib and its potential side effects.
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institution Kabale University
issn 2234-943X
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publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-cfd33303f0ea463bb7d93bab386cf5dd2025-08-20T03:56:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.15442781544278PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinibYingfang Feng0Yuan Gao1Shaochuan Liu2Tingting Qin3Yan Zhang4Jing Wang5Kai Li6Department of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Oncology, Tianjin Haihe Hospital, Tianjin, ChinaDepartment of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Thoracic Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaBackgroundImmunotherapy plays a crucial role in the treatment of tumors. However, few studies have investigated the relationship between the expression of Programmed Cell Death Ligand 1 (PD-L1, CD274) in microvascular endothelial cells (MECs), including blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and immune cell infiltration within tissues.MethodsIn our study, we utilized data from The Cancer Genome Atlas, a mouse subcutaneous xenograft model, and immunofluorescence and immunohistochemical staining to investigate the relationship between PD-L1 expression in melanoma MECs at different tumor stages and the infiltration of CD8+ T cells in tumor and normal organs, under conditions with and without anlotinib treatment.ResultsWe found that PD-L1 expression was upregulated in tumor MECs, while anlotinib downregulated PD-L1 expression in both tumor and normal tissue MECs, corresponding with increased infiltration of CD8+ T cells in the tissues. Additionally, the antitumor effect of anlotinib was most pronounced when administered during the mid-stage of tumor development.ConclusionsThis study evaluated the most effective timing for anlotinib to downregulate PD-L1 expression in tumor and normal tissues to promote immune infiltration. Our findings may offer valuable insights for the clinical use of anlotinib and its potential side effects.https://www.frontiersin.org/articles/10.3389/fonc.2025.1544278/fullanlotinibPD-L1microvascular endothelial cellsimmune checkpointsmelanoma
spellingShingle Yingfang Feng
Yuan Gao
Shaochuan Liu
Tingting Qin
Yan Zhang
Jing Wang
Kai Li
PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
Frontiers in Oncology
anlotinib
PD-L1
microvascular endothelial cells
immune checkpoints
melanoma
title PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
title_full PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
title_fullStr PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
title_full_unstemmed PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
title_short PD-L1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
title_sort pd l1 expression in microvascular endothelial cells predicts the efficacy and side effects of anlotinib
topic anlotinib
PD-L1
microvascular endothelial cells
immune checkpoints
melanoma
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1544278/full
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