| Autor: |
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. |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Science advances, vol. 8, no. 23, pp. eabl5162 |
| ISSN: |
2375-2548 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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