%0 Journal Article
%T Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1+ T lymphocyte niches through a feed-forward loop.
%A Hua Y
%A Vella G
%A Rambow F
%A Allen E
%A Antoranz Martinez A
%A Duhamel M
%A Takeda A
%A Jalkanen S
%A Junius S
%A Smeets A
%A Nittner D
%A Dimmeler S
%A Hehlgans T
%A Liston A
%A Bosisio FM
%A Floris G
%A Laoui D
%A Hollmén M
%A Lambrechts D
%A Merchiers P
%A Marine JC
%A Schlenner S
%A Bergers G
%J Cancer Cell
%V 40
%N 12
%D 12 2022 12
%M 36423635
%F 38.585
%R 10.1016/j.ccell.2022.11.002
%X The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation 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 aggregates develop remains poorly understood. By employing single-cell transcriptomics, endothelial fate mapping, 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/LTβR) 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.