Tumor-infiltrating Lymphocytes Expression in Stage IIIc/IV of High-grade Serous Ovarian Cancer: Variation with Neoadjuvant Chemotherapy and Prognostic Value

Abstract

Background: Ovarian cancer is a malignancy with a complex immune suppressive microenvironment mediated by the recruitment or induction of cluster differentiation factor 4+ (CD4+) regulatory T cells. The purpose of this study was to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIc/IV of High-Grade Serous Ovarian Carcinoma (HGSC), and its relationship to treatment response. Patients and Methods: We retrospectively identified 33 patients diagnosed with HGSC and treated with neoadjuvant platinum-paclitaxel from 2005-2014. Pre-and post-neoadjuvant treatment tissue samples were submitted to immunohistochemical analyses with anti-CD3, CD4 and CD8 antibodies for the identification of tumor-infiltrating lymphocytes (TILs). The staining results were analyzed and were blindly evaluated with respect to clinical features. Pathological response classification to NACT was made according to Steffen Bohm. Results: The mean age of patients was 63.44 years (46.53-84.14). Germline BRCA1/2-mutation status was negative in 58.82% of patients (10/17); BRCA1/2-mutation was positive in 11.76 %(2/17); and a variant of uncertain significance was found in 29.41 %(5/17). The majority of patients (78.8%) were stage IIIc. The area under the ROC curve of post-surgery TILs for complete pathological response was: CD4 (epithelial):