Prognostic Relevance of T Regulatory Cells in Patients with Advanced-Stage Serous Carcinoma Ovary

Abstract

Purpose: Despite improved treatment options, recurrence rates remain high in ovarian cancer. Tumor microenvironment, particularly T cells, plays an important role in its natural history. The present study was conducted to study the kinetics of T cell subsets in homogenous population of advanced-stage ovarian cancer patients of serous histology with reference to treatment and outcome. Methods: We assessed the frequencies of CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs, CD4+ CD25^{intermediate to high} FOXP3+ CD127^low) and natural killer cells in peripheral blood at baseline (n = 41) and post-treatment (n = 27) in the patients and compared it with blood of healthy controls (n = 15). The ascitic fluid of 12 of these patients was compared with ascitic fluid of patients with cirrhotic liver disease (n = 5). Results: Higher numbers of Tregs, CD8+ T cells and higher Treg/CD4 ratio and reduced numbers of CD4+ T cells and reduced CD4/CD8 ratio were observed in patients as compared to controls. An increase in total number of T cells was observed with treatment, while no change in frequency of any lymphocyte subset was evident. Conclusions: These results support previous studies exhibiting an increase in Tregs in ovarian cancer patients. Unchanged levels of T cell subsets subsequent to treatment suggest that they may be resistant to reset to healthy control homeostatic levels with standard chemotherapeutic treatments. Lower CD4 levels, higher CD8 levels, altered CD4/CD8 ratio and T cell subsets call for evaluation of role of immunomodulating agents or Treg-targeted immunotherapy in the treatment of advanced-stage serous carcinoma ovary.