Hua, Yichao and Vella, Gerlanda and Rambow, Florian and Allen, Elizabeth and Martinez, Asier Antoranz and Duhamel, Marie and Takeda, Akira and Jalkanen, Sirpa and Junius, Steffie and Smeets, Ann and Nittner, David and Dimmeler, Stefanie and Hehlgans, Thomas and Liston, Adrian and Bosisio, Francesca Maria and Floris, Giuseppe and Laoui, Damya and Hollmen, Maija and Lambrechts, Diether and Merchiers, Pascal and Marine, Jean-Christophe and Schlenner, Susan and Bergers, Gabriele (2022) Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1(+) T lymphocyte niches through a feed-forward loop. CANCER CELL, 40 (12). 1600-+. ISSN 1535-6108, 1878-3686
Full text not available from this repository. (Request a copy)Abstract
The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the forma-tion of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral and cellular immune responses against cancers, is associated with good prognosis, and they have recently been detected in immune checkpoint blockade (ICB)-responding patients. However, how these lymphoid aggre-gates develop remains poorly understood. By employing single-cell transcriptomics, endothelial fate map-ping, and functional multiplex immune profiling, we demonstrate that antiangiogenic immune-modulating therapies evoke transdifferentiation of postcapillary venules into inflamed high-endothelial venules (HEVs) via lymphotoxin/lymphotoxin beta receptor (LT/LTbR) signaling. In turn, tumor HEVs boost intratumoral lymphocyte influx and foster permissive lymphocyte niches for PD1(-) and PD1(+)TCF1(+) CD8 T cell progenitors that differentiate into GrzB(+)PD1(+) CD8 T effector cells. Tumor-HEVs require continuous CD8 and NK cell -derived signals revealing that tumor HEV maintenance is actively sculpted by the adaptive immune system through a feed-forward loop.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | P-SELECTIN; TRAFFICKING; VASCULATURE; EXPRESSION; DIVERSITY; SOFTWARE; LIGANDS; VENULES; ENTRY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2023 07:40 |
| Last Modified: | 29 Jan 2024 14:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58674 |
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