biostudies-literatureDai ZShanghai Municipal Science and Technology Major ProjectClinical Research Plan of Shanghai Hospital Development CenterNational Natural Science Foundation of ChinaClinical and Scientific Innovation Project of Shanghai Hospital Development CenterNational Key Research and Development Program of ChinaXuhui District Artificial Intelligence Medical Hospital Cooperation Projectthe Scientific Innovation Project of Shanghai Education Committee61https://www.ebi.ac.uk/biostudies/studies/S-EPMC10908625biostudies-literatureUnknown73(4)<h4>Background</h4>Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion.<h4>Methods</h4>We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models.<h4>Results</h4>The rCancer immunology, immunotherapy : CIIEctopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma.PMC1090862521JC140150082072693, 81902417, 82172884, U21A20374SHDC2020CR1006ASHDC120181092020YFA08032022019-01-07-00-07-E000572021-011Zou XWang RTasiheng YMa MLin XChen YWang XLiu CYan YDai ZCheng HYu XfalseEctopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma.<h4>Background</h4>Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion.<h4>Methods</h4>We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models.<h4>Results</h4>The r2024-01-01T00:00:00Z2024 Mar2025-04-22T15:28:04.574Z2025-04-06T01:24:54.739ZS-EPMC109086253843026710.1007/s00262-024-03648-y