Ovarian cancer is a malignancy with a complex immune suppressive microenvironment mediated by the recruitment or induction of CD4+ regulatory T cell. 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 (HGSOC), and its relationship to treatment response.
We retrospectively identified 33 patients diagnosed with HGSOC 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). Pathological response classification to NACT was made according to Steffen Bohm (JCO 2015). Response score system (CRS) was explicitly defined (CRS-1; No or minimal tumor response, CRS-2; Appreciable tumor response amid viable tumor that is readily identifiable, CRS-3; Complete or near-complete response).
The average age of patients was 63.44 years (46.53-84.14). BRCA-mutation status was negative in 78.8% of patients (26/33); BRCA-mutation was positive in 6.1% (2/33); and variant of uncertain significance was found in 15.1% (5/33). The majority of patients (78.8%) were stage IIIc. The area under the ROC curve of post-surgery TILs for complete pathological response were: CD4 (epithelial): [0.73 (0.5; 0.97), p: 0.084]; CD4 (stromal): [0.74 (0.51; 0.97), p: 0.077] and CD8 (epithelial): [0.81 (0.63; 1.0), p: 0.02]. The expression of epithelial CD4 TILs in pre-surgery samples (≤ 0.5 [OR: 0.7(0.01; 0.86), p: 0.038]) and epithelial CD8 TILs in post-surgery samples (≤ 5.4 [OR: 0.1(0.01; 1.19, p: 0.06]) proved to be a marker of good prognosis for pathological response. Survival analysis demonstrated that the expression of epithelial CD3 ≤ 4.3 in pre-surgery samples is a marker of poor prognosis.
The high number of tumor-infiltrating lymphocytes in post-surgery samples was significantly associated with higher rates of complete pathological response and better prognosis. It is convenient to carry out further and multicentric studies to validate these results.
Clinical trial identification
Legal entity responsible for the study
Hospital 12 de Octubre.
All authors have declared no conflicts of interest.