Halama, NielsNielsHalamaZoernig, InkaInkaZoernigBerthel, AnnaAnnaBerthelKahlert, ChristophChristophKahlertKlupp, FeeFeeKluppSuarez-Carmona, MeggyMeggySuarez-CarmonaSuetterlin, ThomasThomasSuetterlinBrand, KarstenKarstenBrandKrauss, JuergenJuergenKraussLasitschka, FelixFelixLasitschkaLerchl, TinaTinaLerchlLuckner-Minden, ClaudiaClaudiaLuckner-MindenUlrich, AlexisAlexisUlrichKoch, MoritzMoritzKochWeitz, JuergenJuergenWeitzSchneider, MartinMartinSchneiderBuechler, Markus W.Markus W.BuechlerZitvogel, LaurenceLaurenceZitvogelHerrmann, ThomasThomasHerrmannBenner, AxelAxelBennerKunz, ChristinaChristinaKunzLuecke, StephanStephanLueckeSpringfeld, ChristophChristophSpringfeldGrabe, NielsNielsGrabeFalk, Christine S.Christine S.FalkJaeger, DirkDirkJaeger2022-05-022022-05-022016-04-11https://resolver.sub.uni-goettingen.de/purl?gro-2/107517The immune response influences the clinical course of colorectal cancer (CRC). Analyzing the invasive margin of human CRC liver metastases, we identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. CCR5 blockade in patient-derived functional in vitro organotypic culture models showed a macrophage repolarization with anti-tumoral effects. These anti-tumoral effects were then confirmed in a phase I trial with a CCR5 antagonist in patients with liver metastases of advanced refractory CRC. Mitigation of tumor-promoting inflammation within the tumor tissue and objective tumor responses in CRC were observed.enjournal_article10.1016/j.ccell.2016.03.00527070705