A multicenter study identifies an immune inflammatory and nutritional prognostic signature in intrahepatic cholangiocarcinoma

BACKGROUND: Immune dysfunction, systemic inflammation, and malnutrition are closely associated with tumor progression and prognosis in intrahepatic cholangiocarcinoma (ICC). This multicenter retrospective study aimed to evaluate the prognostic value of immune-inflammatory-nutritional biomarkers and to establish a novel cholangiocarcinoma immune-inflammatory-nutritional score (CIINS). METHODS: A total of 284 ICC patients who underwent curative surgical resection at three medical centers were retrospectively analyzed and divided into a training cohort (n = 182) and a validation cohort (n = 102). Twelve immune, inflammatory, and nutritional biomarkers derived from routine preoperative blood tests were assessed. The CIINS was constructed using least absolute shrinkage and selection operator Cox regression. Nomograms integrating CIINS with independent clinicopathological factors were developed to predict overall survival (OS) and progression-free survival (PFS). Model performance was evaluated using time-dependent receiver operating characteristic curves, calibration plots, and decision curve analysis. RESULTS: The CIINS consisted of four biomarkers: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, neutrophil-to-albumin ratio, and prognostic nutritional index. Patients were stratified into high- and low-CIINS groups using the median value. High CIINS was significantly associated with poorer OS and PFS in both the training (both p < 0.001) and validation cohorts (OS: p = 0.006; PFS: p = 0.007). Elevated CIINS correlated with obstructive jaundice, increased CA19-9 levels, and advanced AJCC TNM stage. Multivariate analysis confirmed CIINS as an independent prognostic factor. CIINS-based nomograms demonstrated good discrimination and calibration for survival prediction. CONCLUSION: CIINS is a simple and clinically applicable prognostic tool for patients with resected ICC, supporting individualized risk stratification and postoperative management.