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Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity.

ABSTRACT: As a first-line treatment, radiotherapy (RT) is known to modulate the immune microenvironment of glioma, but it is unknown whether the meningeal lymphatic vessel (MLV)-cervical lymph node (CLN) network regulates the process or influences RT efficacy. Here, we show that the MLV-CLN network contributes to RT efficacy in brain tumors and mediates the RT-modulated anti-tumor immunity that is enhanced by vascular endothelial growth factor C (VEGF-C). Meningeal lymphatic dysfunction impaired tumor-derived dendritic cell (DC) trafficking and CD8⁺ T cell activation after RT, whereas tumors overexpressing VEGF-C with meningeal lymphatic expansion were highly sensitive to RT. Mechanistically, VEGF-C-driven modulation of RT-triggered anti-tumor immunity was attributed to C-C Motif Chemokine Ligand 21 (CCL21)-dependent DC trafficking and CD8⁺ T cell activation. Notably, delivery of VEGF-C mRNA significantly enhanced RT efficacy and anti-tumor immunity in brain tumors. These findings suggest an essential role of the MLV-CLN network in RT-triggered anti-tumor immunity, and highlight the potential of VEGF-C mRNA for brain tumor therapy.

SUBMITTER: Zhou C

PROVIDER: S-EPMC9159979 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity.

Zhou Changping C Ma Lu L Xu Han H Huo Yingqing Y Luo Jincai J

Cell research 20220317 6

As a first-line treatment, radiotherapy (RT) is known to modulate the immune microenvironment of glioma, but it is unknown whether the meningeal lymphatic vessel (MLV)-cervical lymph node (CLN) network regulates the process or influences RT efficacy. Here, we show that the MLV-CLN network contributes to RT efficacy in brain tumors and mediates the RT-modulated anti-tumor immunity that is enhanced by vascular endothelial growth factor C (VEGF-C). Meningeal lymphatic dysfunction impaired tumor-der ...[more]

PMID: 35301438

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Dataset Information

Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity.

Publications

Meningeal lymphatics regulate radiotherapy efficacy through modulating anti-tumor immunity.

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