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IFN-γ-dependent tumor-antigen cross-presentation by lymphatic endothelial cells promotes their killing by T cells and inhibits metastasis

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Item Type:Article
Title:IFN-γ-dependent tumor-antigen cross-presentation by lymphatic endothelial cells promotes their killing by T cells and inhibits metastasis
Creators Name:Garnier, L., Pick, R., Montorfani, J., Sun, M., Brighouse, D., Liaudet, N., Kammertoens, T., Blankenstein, T., Page, N., Bernier-Latamani, J., Tran, N.L., Petrova, T.V., Merkler, D., Scheiermann, C. and Hugues, S.
Abstract:Tumor-associated lymphatic vessels promote metastasis and regulate antitumor immune responses. Here, we assessed the impact of cytotoxic T cells on the local lymphatic vasculature and concomitant tumor dissemination during an antitumor response. Interferon-γ (IFN-γ) released by effector T cells enhanced the expression of immunosuppressive markers by tumor-associated lymphatic endothelial cells (LECs). However, at higher effector T cell densities within the tumor, T cell-based immunotherapies induced LEC apoptosis and decreased tumor lymphatic vessel density. As a consequence, lymphatic flow was impaired, and lymph node metastasis was reduced. Mechanistically, T cell-mediated tumor cell death induced the release of tumor antigens and cross-presentation by tumor LECs, resulting in antigen-specific LEC killing by T cells. When LECs lacked the IFN-γ receptor expression, LEC killing was abrogated, indicating that IFN-γ is indispensable for reducing tumor-associated lymphatic vessel density and drainage. This study provides insight into how cytotoxic T cells modulate tumor lymphatic vessels and may help to improve immunotherapeutic protocols.
Keywords:Neoplasm Antigens, Cross-Priming, Endothelial Cells, Interferon-gamma, Lymphatic Metastasis
Source:Science Advances
ISSN:2375-2548
Publisher:American Association for the Advancement of Science
Volume:8
Number:23
Page Range:eabl5162
Date:8 June 2022
Official Publication:https://doi.org/10.1126/sciadv.abl5162
PubMed:View item in PubMed

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