Programmed Death Ligand 1 (PD-L1) Expression and CD8 + Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy

Abstract

To investigate the prevalence and prognostic significance of programmed death ligand-1 (PD-L1) expression and CD8 + tumor-infiltrating lymphocytes (TILs) in gynecologic carcinosarcoma, 81 cases (68 uterine, 12 ovarian, and 1 fallopian tube) were immunostained with PD-L1 and CD8 using tissue microarrays (3 mm core diameter) from intratumoral areas with the highest TILs. Tumor proportion score (TPS) ≥1% and combined positive score (CPS) ≥1 were considered positive for PD-L1. CD8 + TILs were counted in each core, and CD8 + TIL density (CD8TILD) was calculated. Cases were classified as CD8 Neg (<1.4/mm 2 CD8TILD), CD8 Pos (≥1.4/mm 2 CD8TILD) and CD8 HIGH (≥14/mm 2 CD8TILD) and grouped into 4 tumor immune microenvironment (TIME) groups: (1) PD-L-1 Pos /CD8 Pos , (2) PD-L1 Neg /CD8 Neg , (3) PD-L1 Pos /CD8 Neg , and (4) PD-L1 Neg /CD8 Pos . PD-L1 expression by TPS and CPS was detected in 19.8% and 39.6% cases, respectively. Kaplan-Meier curves with log-rank analysis showed that higher density of CD8 + TILs were associated with longer overall survival (OS) ( P =0.05 for CD8 Pos and P =0.014 for CD8 HIGH ), and CD8 HIGH status was associated with longer OS irrespective of tumor stage ( P =0.045, hazard ratio: 0.11, 95% confidence interval: 0.014-0.951). Thirty-three percent of patients belonged to TIME group 1. PD-L1 expression and TIME groups were not associated with OS or progression-free survival. We found that high density of CD8 + TILs is an independent indicator of better OS. In 33% cases PD-L1 expression is associated with increased CD8 + TILs ("acquired immune evasion" pattern of PD-L1 expression), hence they may benefit from anti PD-1/PD-L1 therapy. PD-L1 expression alone and TIME groups do not affect survival in gynecologic carcinosarcoma.