Development and Validation of an Immune Prognostic Index Related to Infiltration of CD4+ and CD8+ T Cells in Colorectal Cancer.

ABSTRACT

Colorectal cancer (CRC) is a highly prevalent cancer worldwide, but treatment outcomes can vary significantly among patients with similar clinical or historical stages. This study aimed to investigate the differences in immune cell abundance associated with malignant progression in CRC patients. We utilized data from patients with CRC obtained from The Cancer Genome Atlas as our training set. To assess immune cell infiltration levels, an immune cell risk score (ICRS) was calculated. Furthermore, we performed network analysis to identify effective T cell-related genes (ETRGs) and subsequently constructed an effective T cell prognostic index (ETPI). The performance of the ETPI was evaluated through external validation using four Gene Expression Omnibus datasets. Additionally, a nomogram analysis and drug sensitivity analysis were conducted to explore the clinical utility of the ETRGs. We also examined the expression of ETRGs in clinical samples. Based on the ICRS, we identified activated CD4+ and CD8+ T cells as protective factors in terms of prognosis. Six ETRGs were identified to develop the ETPI, which exhibited remarkable prognostic performance. In the external validation of immunotherapy, the low ETPI group demonstrated a significantly lower recurrence rate. To optimize therapeutic strategies, we developed a nomogram. Notably, patients with different ETPI values exhibited varying responses to tumor pathway inhibitors. Finally, we observed higher protein expression of certain ETRGs in normal tissues compared to tumors. Our findings suggest that the ETPI may contribute to the precise selection of patients based on tumor microenvironment and key genomic landscape interactions, thereby optimizing drug benefits and informing clinical strategies in future.