| First Author | Garnier L | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 23 | Pages | eabl5162 |
| PubMed ID | 35675399 | Mgi Jnum | J:328672 |
| Mgi Id | MGI:7293796 | Doi | 10.1126/sciadv.abl5162 |
| Citation | Garnier L, et al. (2022) IFN-gamma-dependent tumor-antigen cross-presentation by lymphatic endothelial cells promotes their killing by T cells and inhibits metastasis. Sci Adv 8(23):eabl5162 |
| abstractText | 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. |
