Fig. 6.

A subset of CCOs has intrinsic immunogenic properties. (A, B) Unsupervised clustering based on HLA-II genes expression in two independent CCO cohorts revealed similar clustering patterns. (C) k-means clustering based on HLA-II genes expression revealed 3 subgroups, which were correlated with HLA-II gene expression levels (Kruskal-Wallis test). HLA-II-k3 subgroup (subgroup with the lowest HLA-II genes expression) resulted in unfavorable prognosis (D) and this prognostic impact was independent of patient age, sex, stage, high proliferative molecular subgroup (k1 subgroup) and tumor immune microenvironment (TIM) status (Multivariate Cox regression analysis) (E). (F) Enriched antigen processing/presentation pathway in CCOs with high HLA-II expression (HLA-II-k1 and HLA-II-k2 subgroups). CCOs belonging to these subgroups had high intrinsic immune-stimulatory gene expression (G) and high HLA class I expression (H). However, the total immune cell infiltration amount in primary tissues was not associated with these subgroups (Wilcoxon rank-sum test) (I). (J) These subgroups (HLA-II-k1 and HLA-II-k2 subgroups) were referred as Ca-IIP group and their characteristics were summarized. (K) There were no significant mutations associated with Ca-IIP (p > 0.05 by logistic regression analysis). (L) Enriched cancer-intrinsic signaling pathways based on Ca-IIP (GSEA analysis) in CCOs. CCO, colorectal cancer organoid; Ca-IIP, Cancer cells with intrinsic immunogenic properties