Identification of a tissue resident memory CD8 T cell-related risk score signature for colorectal cancer, the association with TME landscapes and therapeutic responses

Abstract

Backgrounds: The tissue resident memory CD8 T cell (Trm) constitutes an important component of the local immunity. In the context of malignant tumors, mounting evidence also supports the potential anti-tumor property of this cell subset. Therefore, identification of Trm marker genes and exploration of the causative effect of Trm in shaping tumor microenvironment (TME) heterogeneity might provide novel insights for the comprehensive management of cancer patients.Methods: By dissecting a single T cell transcriptome dataset, we acquired marker genes for Trm, which were latter applied to bulk RNA sequencing profiles of two large colorectal cancer (CRC) patient cohorts downloaded from TCGA and GEO databases. First, colorectal cancer patients were divided into different Trm clusters using consensus clustering algorithm. Then, we established a Trm-related gene (TRMRG) risk score signature and tested its efficacy in predicting prognosis for colorectal cancer patients. Moreover, a sequence of rigorous and robust analyses were also carried out to investigate the potential role of Trm-related gene risk score in tumor microenvironment remodeling and therapeutic utility of it in colorectal cancer treatment.Results: A total of 49 Trm marker genes were identified by analyzing single cell RNA sequencing profiles. First, colorectal cancer patients were successfully classified into two Trm clusters with significant heterogeneity in functional enrichment patterns and tumor microenvironment landscapes. Then, we developed a Trm-related gene risk score signature and divided patients into different risk levels. High risk patients were characterized by attenuated immunogenicity, weakened sensitivity to immunotherapy, as well as adverse clinical outcomes. While low risk patients with advantages in survival exhibited increased immunogenicity, stronger metabolic activity and improved immunotherapeutic responses.Conclusion: Through combinatorial analysis of single cell and bulk RNA sequencing data, the present study identified Trm to play a non-negligible role in regulating the complexity and heterogeneity of tumor microenvironment for colorectal cancer. Moreover, the Trm-related gene risk score signature developed currently was corroborated to be tightly correlated with prognosis and therapeutic responses of colorectal cancer patients, thus exhibiting potential application value for clinical practice.

A novel sphingolipid metabolism-related long noncoding RNA signature predicts the prognosis, immune landscape and therapeutic response in pancreatic adenocarcinoma

“…Although risk stratification based on the SMLs can better predict the survival and clinical outcomes of patients with PAAD, it cannot distinguish populations with different TIME characteristics. Studies have shown that tumor subgroups derived from consensus clustering analysis have different TIME characteristics and impact immunotherapy response [ [66] , [67] , [68] ]. Accordingly, we performed a consensus clustering analysis based on the constructed SMLs, dividing the TCGA-PAAD cohort into two clusters to further explore the differences in clinical outcomes and the TIME of patients in different subtypes.…”

Establishment of a Seven-Gene Signature Associated with CD8+ T Cells through the Utilization of Both Single-Cell and Bulk RNA-Sequencing Techniques in Clear Cell Renal Cell Carcinoma

“…To comprehend the pathways and biological roles linked to the DEGs associated with CD8 + T cells, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using the “clusterprofiler” (version 4.8.1) package [ 43 , 44 ].…”

Tissue-Resident Memory T Cells in Gastrointestinal Cancers: Prognostic Significance and Therapeutic Implications

“…The number of CD103+/CD8+ tumor-infiltrating lymphocytes (TILs) is a good prognostic and predictive factor for overall and relapse-free survival in patients with CRC [ 43 ]. Based on a combined analysis of single-cell and bulk RNA-sequencing data, the Trm-related gene risk score was closely correlated with the prognosis and treatment response in patients with CRC [ 52 ]. The percentage of resident memory CD103-expressing CD8+ and γδTCR+ intraepithelial lymphocytes was markedly reduced in the left and right colon of patients with familial adenomatous polyposis compared with healthy controls [ 53 ].…”