Fig. 1

Subtyped CIC structures are associated with the prognosis of patients with resectable PDAC. a Representative images for the 4 CIC subtypes identified in human PDAC tissues. TiT: tumor cell in tumor cell; LiT: leukocyte in tumor cell; MiT: macrophage in tumor cell; TiM: tumor cell in macrophage; scale bars: 5 μm. b–d Profiles of CIC subtypes depicted for all CIC counts (b), for outer cell identities (c), and for inner cell identities (d) in both discovery and validation cohorts. CD68−: negative in CD68. CD68+: positive in CD68. CDs−: negative in both CD68 and CD45. e Kaplan–Meier plotting of overall survival curves for indicated variables in combined cohorts of patients, and CIC structures are associated with overall survival of PDAC patients. f Multivariate analysis consistently identified L/MiT, the heterotypic CIC subtype, as an independent prognostic factor for PDAC patients across discovery cohort, validation cohort and combined cohort as well. g Nomogram analysis with 5 independent prognostic factors (histological grade, N, M, and TNM stage, and L/MiT) identified L/MiT as the prominent prognostic contributor, as indicated by the bar length, at the time point of 14 month-survival in the combined cohorts of patients. tpoints: total points. h The AUC calculation of the prediction performance in the combined cohorts of patients in the presence or absence (w/o) of L/MiT. The inclusion of L/MiT increases survival prediction performance. i Multivariate analysis of prognostic values of L/MiT and TNM staging stratified by TNM stage, grade, age and sex, respectively, in combined cohort of PDAC patients. L/MiT preferentially impacts younger female patients of early resectable PDAC. j–m AUC analysis in combined cohort of patients stratified by TNM stage (I + II vs. III + IV) (j), histological grade (1 + 2 vs. 3) (k), age (≤ 60 vs. >60) (l), and sex (female vs male) (m). L/MiT plays dominant role in young female patients with resectable PDAC