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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: |
Garnier, L.  ORCID: https://orcid.org/0000-0003-4006-5741, Pick, R. ORCID: https://orcid.org/0000-0001-9785-8481, Montorfani, J. ORCID: https://orcid.org/0000-0001-9028-1595, Sun, M., Brighouse, D., Liaudet, N. ORCID: https://orcid.org/0000-0002-0749-5857, Kammertoens, T. ORCID: https://orcid.org/0000-0003-3309-5141, Blankenstein, T. ORCID: https://orcid.org/0000-0002-3357-4321, Page, N., Bernier-Latamani, J., Tran, N.L., Petrova, T.V. ORCID: https://orcid.org/0000-0002-0563-6521, Merkler, D. ORCID: https://orcid.org/0000-0002-0247-2007, Scheiermann, C. ORCID: https://orcid.org/0000-0002-9212-0995 and Hugues, S. ORCID: https://orcid.org/0000-0002-1031-5909
|
| 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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