Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1⁺ T lymphocyte niches through a feed-forward loop.

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

SUBMITTER: Hua Y 

PROVIDER: S-EPMC9899876 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature