Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node

Abstract The lymphatic system plays complex, often contradictory, roles in many cancers, including melanoma; these roles include contributions to tumor cell metastasis and immunosuppression in the tumor microenvironment as well as generation of antitumor immunity. Advancing our understanding of lymp...

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Main Authors: Lauren N. Liebman, Yang Shen, Zachary S. Buchwald, Zhanna Nepiyushchikh, Zhiming Qi, Andrés J. García, J. Brandon Dixon
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-85670-3
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author Lauren N. Liebman
Yang Shen
Zachary S. Buchwald
Zhanna Nepiyushchikh
Zhiming Qi
Andrés J. García
J. Brandon Dixon
author_facet Lauren N. Liebman
Yang Shen
Zachary S. Buchwald
Zhanna Nepiyushchikh
Zhiming Qi
Andrés J. García
J. Brandon Dixon
author_sort Lauren N. Liebman
collection DOAJ
description Abstract The lymphatic system plays complex, often contradictory, roles in many cancers, including melanoma; these roles include contributions to tumor cell metastasis and immunosuppression in the tumor microenvironment as well as generation of antitumor immunity. Advancing our understanding of lymphatic vessel involvement in regulating tumor growth and immune response may provide new therapeutic targets or treatment plans to enhance the efficacy of existing therapies. We utilized a syngeneic murine melanoma model in which we surgically disrupted the lymphatic vessel network draining from the tumor to the tumor-draining lymph node (TDLN) while leaving the TDLN intact. Although transport of lymphatic-specific molecular weight tracers to the TDLN remains present after surgery, disruption of the tumor-draining lymphatic vessels results in decreased local tumor control, as reflected in an increase in the rate of tumor growth and reduction in effector-like T cell infiltration into the tumor. Our findings suggest that preservation of the functional tumor-draining lymphatic network may be essential in promoting a robust antitumor immune response.
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spelling doaj-art-67f02ac1a2e6418cb9d88973dda00c602025-02-02T12:19:20ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-85670-3Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph nodeLauren N. Liebman0Yang Shen1Zachary S. Buchwald2Zhanna Nepiyushchikh3Zhiming Qi4Andrés J. García5J. Brandon Dixon6Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of TechnologyWinship Cancer Institute, Emory UniversityWinship Cancer Institute, Emory UniversityGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of TechnologyWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of TechnologyGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of TechnologyWallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of TechnologyAbstract The lymphatic system plays complex, often contradictory, roles in many cancers, including melanoma; these roles include contributions to tumor cell metastasis and immunosuppression in the tumor microenvironment as well as generation of antitumor immunity. Advancing our understanding of lymphatic vessel involvement in regulating tumor growth and immune response may provide new therapeutic targets or treatment plans to enhance the efficacy of existing therapies. We utilized a syngeneic murine melanoma model in which we surgically disrupted the lymphatic vessel network draining from the tumor to the tumor-draining lymph node (TDLN) while leaving the TDLN intact. Although transport of lymphatic-specific molecular weight tracers to the TDLN remains present after surgery, disruption of the tumor-draining lymphatic vessels results in decreased local tumor control, as reflected in an increase in the rate of tumor growth and reduction in effector-like T cell infiltration into the tumor. Our findings suggest that preservation of the functional tumor-draining lymphatic network may be essential in promoting a robust antitumor immune response.https://doi.org/10.1038/s41598-025-85670-3
spellingShingle Lauren N. Liebman
Yang Shen
Zachary S. Buchwald
Zhanna Nepiyushchikh
Zhiming Qi
Andrés J. García
J. Brandon Dixon
Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node
Scientific Reports
title Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node
title_full Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node
title_fullStr Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node
title_full_unstemmed Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node
title_short Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node
title_sort lymphatic vessel network injury reduces local tumor control despite preservation of the tumor draining lymph node
url https://doi.org/10.1038/s41598-025-85670-3
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