Personalized Immunotherapy Approaches for Enhancing T-Cell Activation and Tumor Destruction in Colorectal Cancer

Abstract

Background: Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide. Traditional treatments have limited efficacy, especially in advanced stages, highlighting the need for innovative approaches like personalized immunotherapy. Objective: This study aims to evaluate personalized immunotherapy approaches, focusing on enhancing T-cell activation and tumor destruction in CRC, to improve therapeutic outcomes and overcome immune evasion mechanisms. Methods: A total of 136 CRC patients were enrolled at the Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, from January 2023 to June 2024. Patients received personalized immunotherapy combining immune checkpoint inhibitors with cancer vaccines and cytokine therapies. Tumor samples were analyzed for tumor mutational burden (TMB), PD-L1 expression, and T-cell infiltration. The clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were tracked. Statistical analysis was conducted using SPSS version 26.0. Results: High TMB correlated with a 67% positive response rate, significantly higher than the 38% in low TMB patients (p-value = 0.02). PD-L1 ≥50% showed a 75% response rate (p-value = 0.01). Patients with high CD8+ T cell infiltration had a 72% response rate (mean ± SD: 45.8% ± 6.5% vs. 35.2% ± 7.3% in low infiltration, p-value = 0.003). Standard deviation for overall treatment response was ±12.4%, indicating substantial variation across patients. Conclusion: Personalized immunotherapy approaches significantly enhance T-cell activation and tumor destruction in CRC, with TMB, PD-L1 expression, and T-cell infiltration being key predictors of treatment response.