Classification of colon adenocarcinoma based on immunological characterizations: Implications for prognosis and immunotherapy

Abstract

Accurate immune molecular typing is pivotal for screening out patients with colon adenocarcinoma (COAD) who may benefit from immunotherapy and whose tumor microenvironment (TME) was needed for reprogramming to beneficial immune-mediated responses. However, little is known about the immune characteristic of COAD. Here, by calculating the enrichment score of immune characteristics in three online COAD datasets (TCGA-COAD, GSE39582, and GSE17538), we identified 17 prognostic-related immune characteristics that overlapped in at least two datasets. We determined that COADs could be stratified into three immune subtypes (IS1–IS3), based on consensus clustering of these 17 immune characteristics. Each of the three ISs was associated with distinct clinicopathological characteristics, genetic aberrations, tumor-infiltrating immune cell composition, immunophenotyping (immune “hot” and immune “cold”), and cytokine profiles, as well as different clinical outcomes and immunotherapy/therapeutic response. Patients with the IS1 tumor had high immune infiltration but immunosuppressive phenotype, IS3 tumor is an immune “hot” phenotype, whereas those with the IS2 tumor had an immune “cold” phenotype. We further verified the distinct immune phenotype of IS1 and IS3 by an in-house COAD cohort. We propose that the immune subtyping can be utilized to identify COAD patients who will be affected by the tumor immune microenvironment. Furthermore, the ISs may provide a guide for personalized cancer immunotherapy and for tumor prognosis.

Investigating gene signatures associated with immunity in colon adenocarcinoma to predict the immunotherapy effectiveness using NFM and WGCNA algorithms

“…Immunotherapy, as one of the most likely therapeutic cures for tumors, is classified into two main categories: immune cell therapy and immune checkpoint therapy, and has been applied in the clinical treatment of a variety of tumors with encouraging therapeutic results [32][33][34][35]. For treating COAD patients, the immune checkpoint-related medications nabolutumab and pablizumab are now being used in clinical trials [36]. Nevertheless, due to a lack of biomarkers and models to predict patient response and prognosis to immunotherapy, low response rates to immunotherapy, and the fact that only some patients indicate treatment, immunotherapy has experienced several challenges in clinical practice [37,38].…”

The prognostic value of the tertiary lymphoid structure in gastrointestinal cancers

“…Recent studies have shown that the formation of TLS is mediated by certain pro-inflammatory cytokines and TNF receptor family members, and involves the participation of fibroblasts, perivascular myofibroblasts, and stromal cells (55). However, in gastrointestinal cancer, a large number of patients have low tumor mutation burden and lack immune cell infiltration, making their tumor microenvironment "cold" and resulting in poor response to emerging therapies targeting the tumor immune microenvironment, such as immunotherapy (56,57). Hooren et al discovered the formation of TLS during the process of transforming the solid tumor immune microenvironment from "cold" to "hot" using a CD40 agonist, and TLS was found to be correlated with increased infiltration of T cells (58).…”

Exploration of prognostic biomarkers in head and neck squamous cell carcinoma microenvironment from TCGA database

“…In recent year, algorithms have been developed to predict tumor purity using gene expression data based on the TCGA database. For example, (36,37), breast cancer (38,39), colorectal cancer (40)(41)(42) and hepatocellular carcinoma (43), which demonstrated that such big-data-based algorithms are effective, although its utility on immune and/or stromal scores in glioblastoma multiforme (GBM) has not been explored in detail.…”