The Relationship of Tumor-infiltrating Lymphocyte Ratio with Histopathological Parameters and Effect on Survival in Colorectal Cancers

Abstract

Introduction: Tumor lymphocyte infiltration demonstrates a positive effect on patient survival in breast cancer, melanoma, renal cell carcinoma, and lung cancer. This study aimed to elucidate the relationship between tumor-infiltrating lymphocyte (TIL) ratio and disease-free survival (DFS) and overall survival (OS) by considering localization, clinical and pathological features, microsatellite instability (MSI) status, mutation status, and demographic data. Method: Patients (n=248) diagnosed with colorectal cancer stages 1, 2, and 3 were analyzed retrospectively. Patients with an Eastern Cooperative Oncology Group performance score of <2 were excluded. Clinical characteristics, age, gender, histopathologic features, TIL ratio, and carcinoembryonic antigen (CEA) level of the patients were recorded. Results: Stage, CEA level, TIL ratio, N stage, T stage, and lymphovascular invasion were statistically significant. Early stage (p=0.019), low CEA level (p≤0.001), high TIL ratio (p=0.046), low N stage (p=0.004), low T stage (p=0.016), and absence of lymphovascular invasion (p=0.037 and p=0.046) were associated with longer DFS. Lymphovascular invasion, N stage, CEA levels, and TIL ratio were analyzed using multivariate analysis. According to the results, the hazard ratio (HR) for the TIL ratio was 1.68 (95% confidence interval (CI): 1.005-2.807; p=0.048), and the HR for the CEA level was 0.49 (95% CI: 0.293-0.846; p=0.01). Conclusion: Regarding the outcomes of this research, the TIL ratio was found to be an effective indicator of DFS, confirmed via multivariate analysis to present a 32% reduction in the risk of recurrence/relapse. The TIL ratio was identified as a prognostic factor beyond the effects of stage, grade, lymphovascular invasion, CEA level, and MSI status. The current data provides substantial evidence to support the ratio’s consideration in staging guidelines.

Keywords

• colorectal cancer
• tumor-infiltrating lymphocytes
• tumor immunology
• immune response
• prognostic factors