biostudies-literatureZabransky DJNCI NIH HHS599-611https://www.ebi.ac.uk/biostudies/studies/S-EPMC12130352biostudies-literatureUnknown82(3)<h4>Background and aims</h4>Isocitrate dehydrogenase 1 ( IDH1 )-mutant cholangiocarcinoma (CCA) is a highly lethal subtype of hepatobiliary cancer that is often resistant to immune checkpoint inhibitor therapies. We evaluated the effects of IDH1 mutations in CCA cells on the tumor immune microenvironment and identified opportunities for therapeutic intervention.<h4>Approach and results</h4>Analysis of 2606 human CCA tumors using deconvolution of RNA-sequencing data identified decreased CD8+ T cell and increased M2-like tumor-associated macrophage (TAM) infiltration in IDH1 -mutant compared to IDH1 wild-type tumors. To model the tumor immune microenvironment of IDH1 -mutant CCA in vivo, we generated an isogenic cell line panel of mouse SB1 CCA cells containing a heterozygous IDH1 R132C (SB1Hepatology (Baltimore, Md.)Tumor-derived CCL2 drives tumor growth and immunosuppression in IDH1- mutant cholangiocarcinoma.PMC12130352P50 CA062924Azad NSZabransky DJDalton WBChhabra YCharmsaz SBaretti MLeatherman JMDavis MLee JWJaffee EMKartalia EFranch-Exposito SOshima KKang MYoung SERastkari NMaru SYarchoan MfalseTumor-derived CCL2 drives tumor growth and immunosuppression in IDH1- mutant cholangiocarcinoma.<h4>Background and aims</h4>Isocitrate dehydrogenase 1 ( IDH1 )-mutant cholangiocarcinoma (CCA) is a highly lethal subtype of hepatobiliary cancer that is often resistant to immune checkpoint inhibitor therapies. We evaluated the effects of IDH1 mutations in CCA cells on the tumor immune microenvironment and identified opportunities for therapeutic intervention.<h4>Approach and results</h4>Analysis of 2606 human CCA tumors using deconvolution of RNA-sequencing data identified decreased CD8+ T cell and increased M2-like tumor-associated macrophage (TAM) infiltration in IDH1 -mutant compared to IDH1 wild-type tumors. To model the tumor immune microenvironment of IDH1 -mutant CCA in vivo, we generated an isogenic cell line panel of mouse SB1 CCA cells containing a heterozygous IDH1 R132C (SB12025-01-01T00:00:00Z2025 Sep2026-06-05T20:43:29.781Z2026-05-21T03:13:05.443ZS-EPMC121303523962620910.1097/HEP.000000000000118510.1097/hep.0000000000001185