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.

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 CD8Neg (<1.4/mm2 CD8TILD), CD8Pos (≥1.4/mm2 CD8TILD) and CD8HIGH (≥14/mm2 CD8TILD) and grouped into 4 tumor immune microenvironment (TIME) groups: (1) PD-L-1Pos/CD8Pos, (2) PD-L1Neg/CD8Neg, (3) PD-L1Pos/CD8Neg, and (4) PD-L1Neg/CD8Pos. 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 CD8Pos and P=0.014 for CD8HIGH), and CD8HIGH 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.