biostudies-literatureBlair ABNational Cancer InstituteNCI NIH HHSSidney Kimmel Comprehensive Cancer CenterNIH5351-5363https://www.ebi.ac.uk/biostudies/studies/S-EPMC6726532biostudies-literatureUnknown25(17)<h4>Purpose</h4>Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid cells has had limited success. Here, we sought to target the myeloid cells through modifying a specific stromal component.<h4>Experimental design</h4>A murine model of metastatic PDAC treated with an irradiated whole-cell PDAC vaccine and PDAC specimens from patients treated with the same type of vaccine were used to assess the immune-modulating effect of stromal hyaluronan (HA) degradation by PEGPH20.<h4>Results</h4>Targeting stroma by degrading HA with PEGPH20 in combination with vaccine decreases CXCL12/CXCR4/CCR7 immunosuppressive signaling axis expression in cancer-associated fibroblasts, myeloid, and CD8⁺ T ceClinical cancer research : an official journal of the American Association for Cancer ResearchDissecting the Stromal Signaling and Regulation of Myeloid Cells and Memory Effector T Cells in Pancreatic Cancer.PMC6726532P30 CA006973T32 CA126607R01 CA197296R01 CA169702K23 CA148964P50 CA062924Saung MTHe JLokker NWolfgang CLCoussens LMBurkhart RABlouw BJaffee EMBlair ABArmstrong TDTsujikawa TZheng LMuth STKim VMfalseDissecting the Stromal Signaling and Regulation of Myeloid Cells and Memory Effector T Cells in Pancreatic Cancer.<h4>Purpose</h4>Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid cells has had limited success. Here, we sought to target the myeloid cells through modifying a specific stromal component.<h4>Experimental design</h4>A murine model of metastatic PDAC treated with an irradiated whole-cell PDAC vaccine and PDAC specimens from patients treated with the same type of vaccine were used to assess the immune-modulating effect of stromal hyaluronan (HA) degradation by PEGPH20.<h4>Results</h4>Targeting stroma by degrading HA with PEGPH20 in combination with vaccine decreases CXCL12/CXCR4/CCR7 immunosuppressive signaling axis expression in cancer-associated fibroblasts, myeloid, and CD8⁺ T ce2019-01-01T00:00:00Z2019 Sep2026-05-04T10:08:43.744Z2020-09-09T07:06:29ZS-EPMC67265323118631410.1158/1078-0432.ccr-18-419210.1158/1078-0432.CCR-18-4192