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-gamma (IFN-gamma) 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-gamma receptor expression, LEC killing was abrogated, indicating that IFN-gamma 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.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Medizin |
Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
ISSN: | 2375-2548 |
Sprache: | Englisch |
Dokumenten ID: | 113536 |
Datum der Veröffentlichung auf Open Access LMU: | 02. Apr. 2024, 07:50 |
Letzte Änderungen: | 02. Apr. 2024, 07:50 |