At diagnosis, tumor-infiltrating lymphocytes (TILs) are prognostic in epithelial ovarian cancer (EOC). We recently demonstrated that neoadjuvant chemotherapy (NACT) significantly increased stromal TILs and stromal TILs remained prognostically significant after NACT. Here, we investigated the impact of NACT on different immune subpopulations and their relationship with clinical outcome.
Tissue microarrays of EOC (145 pre-NACT, 139 post-NACT, including 83 matched samples) were analyzed for CD3+,CD8+ and FOXP3+ by immunohistochemistry. Stromal TILs scored as percentage of stromal area, intraepithelial TILs as number of TILs in contact with tumor cells/HPF. Differences were evaluated by Mann-Whitney or Wilcoxon-signed-rank for unpaired or paired analyses, respectively and by Log-rank for PFS and OS.
NACT significantly increased stromal CD3 + (p = 0.005) and CD8 + (p = 0.009) and intraepithelial CD8 + (p = 0.02) infiltration in unmatched samples and remained significant among paired samples for stromal CD3+ and CD8 + (p = 0.03 and p = 0.009). Neither CD3+ nor CD8+ expression correlated with outcome at diagnosis or post-NACT, however reduced accumulation of FOXP3+ post-NACT (
NACT has a significant impact on the balance of cytotoxic versus suppressive T cells and a high ratio of CD8+/FOXP3+ post-NACT was most significantly associated with improved PFS and OS. Whether this could select patients for immune therapies in the post-operative setting should be investigated.
Clinical trial identification
Legal entity responsible for the study
Institut Gustave Roussy
INCA and MERUS
All authors have declared no conflicts of interest.