Advances in immunotyping of colorectal cancer

Immunotherapy has transformed treatment for various types of malignancy. However, the benefit of immunotherapy is limited to a minority of patients with mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) (dMMR-MSI-H) colorectal cancer (CRC). Understanding the complexity and heterogeneity of the tumor immune microenvironment (TIME) and identifying immune-related CRC subtypes will improve antitumor immunotherapy. Here, we review the current status of immunotherapy and typing schemes for CRC. Immune subtypes have been identified based on TIME and prognostic gene signatures that can both partially explain clinical responses to immune checkpoint inhibitors and the prognosis of patients with CRC. Identifying immune subtypes will improve understanding of complex CRC tumor heterogeneity and refine current immunotherapeutic strategies

Action of m6A-related gene signatures on the prognosis and immune microenvironment of colonic adenocarcinoma

N6-methyladenosine (m6A) modification in human tumor cells exerts considerable influence on crucial processes like tumorigenesis, invasion, metastasis, and immune response. This study aims to comprehensively analyze the impact of m6A-related genes on the prognosis and immune microenvironment (IME) of colonic adenocarcinoma (COAD). Public data sources, predictive algorithms identified m6A-related genes and differential gene expression in COAD. Subtype analysis and assessment of immune cell infiltration patterns were performed using consensus clustering and the CIBERSORT algorithm. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis determined gene signatures. Independent prognostic factors were identified using univariate and multivariate Cox proportional hazards models. The findings indicate that 206 prognostic m6A-related DEGs contribute to the m6A regulatory network along with 8 m6A enzymes. Based on the expression levels of these genes, 438 COAD samples from The Cancer Genome Atlas (TCGA) were classified into 3 distinct subtypes, showing marked differences in survival prognosis, clinical characteristics, and immune cell infiltration profiles. Subtype 3 and 2 displayed reduced levels of infiltrating regulatory T cells and M0 macrophages, respectively. A six-gene signature, encompassing KLC3, SLC6A15, AQP7 JMJD7, HOXC6, and CLDN9, was identified and incorporated into a prognostic model. Validation across TCGA and GSE39582 datasets exhibited robust predictive specificity and sensitivity in determining the survival status of COAD patients. Additionally, independent prognostic factors were recognized, and a nomogram model was developed as a prognostic predictor for COAD. In conclusion, the six target genes governed by m6A mechanisms offer substantial potential in predicting COAD outcomes and provide insights into the unique IME profiles associated with various COAD subtypes

Single-cell transcriptome analysis reveals T population heterogeneity and functions in tumor microenvironment of colorectal cancer metastases

Cell mediated immune escape, a microenvironment factor, induces tumorigenesis and metastasis. The purpose of this study was to display the characteristics of T cell populations in immune microenvironments for colorectal cancer (CRC) metastasis. Unsupervised cluster analysis was conducted to identify functionally distinct T cell clusters from 3,003 cells in peripheral blood and 4,656 cells in tissues. Subsequently, a total of 8 and 4 distinct T cell population clusters were identified from tumor tissue and peripheral blood, respectively. High levels of CD8+TEX, CD4+TRM, TH1-like T cells, CD8+TEM, tumor-Treg from tissues, and CD4+TN from peripheral blood are essential components of immune microenvironment for the prediction of CRC metastasis. Moreover, exhausted T cells are characterized by higher expression of multiple inhibitory receptors, including PDCD1 and LAG3. Some genes such as PFKFB3, GNLY, circDCUN1D4, TXNIP and NR4A2 in T cells of cluster were statistically different between CRC metastasis and non-metastasis. The ligand-receptor interactions identified between different cluster cells and metastases-related DEGs identified from each cluster revealed that the communications of cells, alterations of functions, and numbers of T subsets may contribute to the metastasis of CRC. The mutation frequency of KiAA1551, ATP8B4 and LNPEP in T cells from tissues and SOR1 from peripheral blood were higher in metastatic CRC than that in non-metastatic CRC. In conclusion, the discovery of differential genes in T cells may provide potential targets for immunotherapy of CRC metastasis and relevant insights into the clinical prediction and prognosis of CRC metastasis

Additional file 1 of Identification of enterotype and its predictive value for patients with colorectal cancer

Supplementary Material