SRP344328 PRJNA777408 lncRNA transcriptome of cancer tissues, adjacent normal tissues and plasma exosomes of patients with intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is an uncommon liver tumor characterized by a high incidence of metastases, infiltration, and relapse, with a higher prevalence rate in Asian countries due to differences in etiology. Liquid biopsy and immunotherapy of ICC are promising translational medical approaches to improve the current situation that the diagnosis is at a late stage and radical surgical resection is difficult. Herein, we investigated the transcriptome of ICC tissues, adjacent normal tissues, and plasma exosomes of Asian ICC patients from Northern (n=7) and Southern (n=7) China. We identified an immunogenic subgroup of Asian ICC distinct from Caucasian ICC, featured by both T cell exhaustion and neutrophil extracellular traps. Up-regulation of immune checkpoints (PD-L1, CTLA-4), elevated regulatory T cell and decreased CD8+ T cell infiltration indicated T cell exhaustion in this subgroup. Increased M1 macrophage infiltration and Neutrophil extracellular traps including neutrophil recruitment, thrombosis by platelets, and the tendency of cancer metastases were also observed. circ-PTPN22 (chr1_113834909_113855049_-) and circ-ADAMTS6 (chr5_65451474_65473952_+) were elevated in ICC tissues and plasma exosomes of this subgroup, associated with PTPN22 and ADAMTS6 up-regulation in T cells and endothelial cells. Our results revealed an Asian immunogenic ICC subgroup featured by T cell exhaustion and neutrophil extracellular trap, potentially treatable with immune checkpoint blockade, and marked by elevated circ-PTPN22 and circ-ADAMTS6 in plasma exosome.