biostudies-literatureSarhan DSjöbergstiftelsenKarolinska InstitutetRobertson FoundationNCI NIH HHSCancerfonden105317https://www.ebi.ac.uk/biostudies/studies/S-EPMC9615326biostudies-literatureUnknown25(11)Immunotherapy for cancer that aims to promote T cell anti-tumor activity has changed current clinical practice, where some previously lethal cancers have now become treatable. However, clinical trials with low response rates have been disappointing for pancreatic ductal adenocarcinoma (PDAC). One suggested explanation is the accumulation of dominantly immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells in the tumor microenvironment (TME). Using retrospectively collected tumor specimens and transcriptomic data from PDAC, we demonstrate that expression of the scavenger receptor MARCO correlates with poor prognosis and a lymphocyte-excluding tumor phenotype. PDAC cell lines produce IL-10 and induce high expression of MARCO in myeloid cells, and this was furtheriScienceTargeting myeloid suppressive cells revives cytotoxic anti-tumor responses in pancreatic cancer.PMC9615326R01 CA258324Carannante VHe FLohr MJBenitez IISchlisio SKarlsson MCIPelicano CHumoud REisinger SHeuchel ROnfelt BLi SBergsland MSarhan DRavetch JVMuhr JWestberg KPalano GDriescher CfalseTargeting myeloid suppressive cells revives cytotoxic anti-tumor responses in pancreatic cancer.Immunotherapy for cancer that aims to promote T cell anti-tumor activity has changed current clinical practice, where some previously lethal cancers have now become treatable. However, clinical trials with low response rates have been disappointing for pancreatic ductal adenocarcinoma (PDAC). One suggested explanation is the accumulation of dominantly immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells in the tumor microenvironment (TME). Using retrospectively collected tumor specimens and transcriptomic data from PDAC, we demonstrate that expression of the scavenger receptor MARCO correlates with poor prognosis and a lymphocyte-excluding tumor phenotype. PDAC cell lines produce IL-10 and induce high expression of MARCO in myeloid cells, and this was further2022-01-01T00:00:00Z2022 Nov2026-05-28T00:36:12.813Z2025-05-29T16:10:57.538ZS-EPMC96153263631058210.1016/j.isci.2022.105317