CD8A and cholangiocarcinoma: This conclusion also mirrors other reports in pancreatic, breast, and bladder cancers, where NETs have been shown to suppress CD8+ T cell recruitment to the TIME.[70, 85, 86] Meanwhile, CD8+ T cell exhaustion was reported to mediate immunotherapy in CCA,[87] as well as other cancers including melanoma, colorectal cancer, and bladder cancer.[88, 89, 90] Hence, we propose that high CXCL6 expression in CCA reduces CD8+ T cell infiltration through NETs formation, eventually causing immunotherapy resistance.