Systematic exploration of the molecular characteristics of CD8 T cells to predict the response to immunotherapy and the prognosis of patients with colon adenocarcinoma.

BACKGROUND

Recently, immunotherapy has been recognized as an innovative treatment with great potential for patients with colon adenocarcinoma (COAD). Although the relationships between immune cells and immune substances are intricate and still unclear, some immune cells and substances could be considered prognostic factors for predicting therapeutic efficacy. To understand the genomic signatures of COAD related to CD8 T cells that could predict the prognosis of patients receiving immunotherapy and to discover new therapeutic targets, we conducted this study.

METHODS

Data were gathered from the TCGA and GEO databases to assess the molecular features of CD8 T cells. We developed a CD8 T-cell score (CD8S) to quantify the population of CD8 T cells in each COAD patient. A thorough analysis of multilevel data was conducted to evaluate overall survival (OS), biological functions, immunological profiles, drug sensitivity, and responses to immunotherapy between the two groups defined by CD8S. Additionally, a series of in vitro experiments were executed to validate the reliability of the signatures associated with CD8 T cells.

RESULTS

CD8S has been shown to be a reliable prognostic factor for COAD according to different patient and subgroup analyses. Through in vitro experiments, we suggested that TSPYL2 may act as an oncogene in COAD. Through functional analysis, a high expression of genes linked to the cell cycle, cytoskeleton, cell adhesion, and various cancer-related pathways was observed in the high CD8S group, which aids in tumor invasion. Moreover, immune analysis reflected immunosuppression in patients with high CD8S. Patients in the low CD8S group were more sensitive to chemotherapy, targeted drugs, and immunotherapy due to higher genetic variants.

CONCLUSION

To better understand the biological characteristics and prognostic significance of CD8 T cells in immunotherapy for COAD, we thoroughly examined the molecular properties of CD8 T cells in COAD and developed a CD8 T-cell model.