Tumor-derived CCL2 drives tumor growth and immunosuppression in IDH1- mutant cholangiocarcinoma.

ABSTRACT:

Background and aims

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.

Approach and results

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 (SB1

SUBMITTER: Zabransky DJ 

PROVIDER: S-EPMC12130352 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature