The Pretreatment Tumor Infiltrating T Lymphocytes (CD8+, CD4+, FOXP3+) and Systemic Neutrophil-Lymphocytes Ratio in Definitively Treated Cervical Cancer Patients: The Correlation to Clinicopathological Factors and Survival

Abstract

Purpose: To evaluate the prognostic potential of pre-treatment tumour infiltrating T lymphocytes (TILs) (CD8+, CD4+, FOXP3+) and systemic neutrophil to lymphocyte ratio (NLR) in predicting the outcome of definitively treated cervical cancer patients.Methods: Both densities of pre-treatment TILs (CD8+, CD4+, FOXP3+) in cervical biopsies and NLR were correlated with clinicopathological parameters. The prognostic value of pre-treatment TILs and NLR for disease free survival (DFS) and overall survival (OS) were assessed using Log rank and Cox regression.Results: The final analysis included 28 had who radical hysterectomy while 20 had definitive concurrent chemoradiation. Elevated CD8+, CD8+/CD4+ and low FOXP3+ were associated with node negative, early stage disease and radical hysterectomies. Conversely, elevated NLR was associated with advanced stages, nodal involvement and definitive chemoradiation. Cox regression multivariate revealed that elevated NLR along with nodal involvement were independently correlated with poor prognosis with hazard ratio (HR 3.06 (95% confidence interval [CI], 3.45-9.24),5.63 (95% CI, 2.61-9.32) for OS and (HR 8.21 (95% CI, 4.21-16.53) and 5.32 (95% CI, 2.37-10.24) for DFS respectively. Additionally, FOXP3+ ≥ 19 and CD8+/CD4+ < 2 were significantly associated with decreased OS (HR 4.37 (95% CI, 2.48-12.37), 2.31 (95% CI, 2.34-9.32) and poorer DFS (HR 3.61 (95% CI, 1.38- 9.32), 4.32 (95% CI,3.12-8.34) respectively.Conclusion: The Pre-treatment NLR, CD8+, FOXP3+ and C8/CD4+ showed a significant association with different clinicopathological prognostic factors in definitively treated cervical cancer patients. Additionally, they may be considered as potential independent prognostic indicators of clinical outcomes.