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

Details

Serval ID
serval:BIB_E6812AD09BD7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IFN-γ-dependent tumor-antigen cross-presentation by lymphatic endothelial cells promotes their killing by T cells and inhibits metastasis.
Journal
Science advances
Author(s)
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., Hugues S.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
10/06/2022
Peer-reviewed
Oui
Volume
8
Number
23
Pages
eabl5162
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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
Antigens, Neoplasm, Cross-Priming, Endothelial Cells/metabolism, Humans, Interferon-gamma/metabolism, Lymphatic Metastasis
Pubmed
Create date
21/06/2022 14:21
Last modification date
15/07/2022 6:35
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