Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival

• DOI: 10.1186/s13046-021-02034-1
• Publication Date: 2021-07-13T07:03:06Z
• Authors: Eun Jeong Cho; Minsuh Kim; Daum Jo; Jihye Kim; Ji-Hye Oh; Hee Chul Chung; Sun-hye Lee; Deokhoon Kim; Sung-Min Chun; Jihun Kim; Hyeonjin Lee; Tae Won Kim; Chang Sik Yu; Chang Ohk Sung; Se Jin Jang
• Keywords: Organoid

The intrinsic immuno-ge7nomic characteristics of colorectal cancer cells that affect tumor biology and shape the immune microenvironment (TIM) are unclear.We developed a patient-derived organoid (CCO) model performed pairwise analysis 87 CCOs their matched primary tumors. TIM type was classified as immuno-active, immuno-exhausted, or immuno-desert.The gene expression profiles, signaling pathways, major oncogenic mutations, histology recapitulated those tumors, but not Two distinct molecular subgroups highly proliferative mesenchymal phenotypes with clinical significance were identified in various pathways. showed variable cancer-specific immune-related genes such encoding HLA-I HLA-II, molecules involved checkpoint activation/inhibition. Among these genes, HLA-II associated favorable patient survival. K-means clustering based on revealed subgroup patients, whom exhibited Intrinsically Immunogenic Properties (Ca-IIP), characterized by high signatures HLA-I, antigen presentation, stimulation. Patients Ca-IIP phenotype had an excellent prognosis, irrespective age, disease stage, type, status. negatively correlated E2F/MYC signaling. Analysis correlation between CCO immuno-genotype microsatellite instability, Wnt/β-catenin signaling, APC/KRAS unfolded protein response pathway linked to FBXW7 mutation cells. However, phenotype.We from large set CCOs. Our findings may provide unprecedented opportunity develop new strategies for optimal stratification this era immunotherapy.