{Reference Type}: Journal Article
{Title}: Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1+ T lymphocyte niches through a feed-forward loop.
{Author}: Hua Y;Vella G;Rambow F;Allen E;Antoranz Martinez A;Duhamel M;Takeda A;Jalkanen S;Junius S;Smeets A;Nittner D;Dimmeler S;Hehlgans T;Liston A;Bosisio FM;Floris G;Laoui D;Hollmén M;Lambrechts D;Merchiers P;Marine JC;Schlenner S;Bergers G;
{Journal}: Cancer Cell
{Volume}: 40
{Issue}: 12
{Year}: 12 2022 12
{Factor}: 38.585
{DOI}: 10.1016/j.ccell.2022.11.002
{Abstract}: 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.