Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy

Abstract

Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular classification system for colorectal cancer (CRC). We obtained data of 1503 CRC patients (training cohort: 488 from The Cancer Genome Atlas; validation cohort: 1015 from the Gene Expression Omnibus). In the training cohort, 42.8% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were subdivided into immune classes. Within the immune class, 53.1% of patients were associated with a worse overall prognosis and belonged to the immune-suppressed subclass, characterized by the activation of stroma-related signatures, genes, immune-suppressive cells, and signaling. The remaining immune class patients belonged to the immune-activated subclass, which was associated with a better prognosis and response to anti-PD-1 therapy. Immune-related subtypes were associated with different copy number alterations, tumor-infiltrating lymphocyte enrichment, PD-1/PD-L1 expression, mutation landscape, and cancer stemness. These results were validated in patients with microsatellite instable CRC. We described a novel immune-related class of CRC, which may be used for selecting candidate patients with CRC for immunotherapy and tailoring optimal immunotherapeutic treatment.

Identification of immune subtypes and their prognosis and molecular implications in colorectal cancer

“…Immunoscore has been constructed to predict CRC prognosis using algorithms such as CIBERSORT [ 17 ] and ESTIMATE [ 18 ]. Previous studies reported better survivals in CRC patients with a low immunoscore or in an immune-activated subclass.…”

PBK/TOPK Is a Favorable Prognostic Biomarker Correlated with Antitumor Immunity in Colon Cancers

“…Given the oncogenic role of PBK/TOPK in the process of tumorigenesis and tumor progression, it is interesting to find that high expression of PBK/TOPK correlates with an improved prognosis in colon cancer. Since tumor infiltrating immune cells contributes to determining the prognosis of colon cancer [ 60 , 61 ], we analyzed the changes in immune profiles including immune cell composition and inflammatory signatures. High PBK/TOPK expression in colon cancer was correlated with an increased infiltration level of cytotoxic immune cells, whereas activated CD8+ T- and NK-cell-infiltrated tumors also exhibited decreased infiltration of Treg cells and M2 macrophages that have immunosuppressive roles in TME.…”

Advances in immunotyping of colorectal cancer

“…Zheng et al. ( 33 ) analyzed data from 488 patients with CRC from the TCGA-COAD dataset (training cohort) and from 1,015 in the GSE39582 ( 61 ), GSE14333 ( 63 ), and GSE17538 ( 65 ) datasets (validation cohorts). They identified immune-related immune-activated, immune-suppressed, and non-immune CRC subtypes using the NMF algorithm based on the top 150 exemplar genes in immune profiles.…”