Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

Flow cytometry analysis of endothelial cells and subsets of exhausted CD8+ T cells in murine tumor models

“…For detailed procedures on tumor models, including cell culture of tumor cell lines, subcutaneous injection of tumor cells and tumor growth monitoring, refer to Asrir et al. (2022) .…”

“…Although separate analysis of specific tumor regions could provide some spatial information, we recommend performing histologic analysis on tumor sections in addition to flow cytometry analysis when investigating tumor immunology. We also recommend the use of dynamic techniques such as intravital microscopy and multiphoton in vivo imaging to better define the functionality of different subsets of ECs and T cells in tumors ( Asrir et al., 2022 ).…”

“…This protocol represents a valuable tool for the analysis of rare subsets of tumor ECs and CD8+ T cells with critical roles in antitumor immunity. For complete details on the use and execution of this protocol, please refer to Asrir et al. (2022) .…”

“…For complete details on the use and execution of this protocol, please refer to Asrir et al. (2022) .…”

Editorial: Tumor Vessels as Directors of the Tumor Microenvironment: New Findings, Current Challenges & Perspectives

“…Seemingly, combination approaches using AAT and anti-PD-L1 therapy showed improved efficiency by counteracting therapy-induced adaptive immunosuppressive pathways, by enhancing the tumor infiltration of T cell via promoting high endothelial venule (HEV) formation ( Allen et al, 2017 ). Indeed, tumor-associated HEVs represent the main site of lymphocytes extravasation upon combined anti-PD-1/anti-CTLA-4 immunotherapy, and it was recently uncovered that LTßR-mediated HEV maturation is crucial to improve the efficacy of these immunotherapies ( Asrir et al, 2022 ). Different targeted approaches meant to foster tumor HEV generation led to promising reinforced efficacy of combination therapy in several cancer entities including pancreatic neuroendocrine tumors ( Johansson-Percival et al, 2017 ), glioblastoma ( He et al, 2018 ), lung metastases ( He et al, 2020 ) but would now require clinical translation.…”