TY - JOUR
T1 - Programmed Death Ligand 1 (PD-L1) Expression and CD8+Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma
T2 - Prognostic Impact and Implications for Therapy
AU - Ordner, Jeffrey
AU - Gutierrez Amezcua, Jose M.
AU - Marcus, Alan
AU - Shukla, Pratibha S.
N1 - Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - 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/mm2CD8TILD), CD8Pos(≥1.4/mm2CD8TILD) and CD8HIGH(≥14/mm2CD8TILD) 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 CD8Posand P=0.014 for CD8HIGH), and CD8HIGHstatus 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.
AB - 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/mm2CD8TILD), CD8Pos(≥1.4/mm2CD8TILD) and CD8HIGH(≥14/mm2CD8TILD) 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 CD8Posand P=0.014 for CD8HIGH), and CD8HIGHstatus 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.
KW - CD8
KW - Gynecologic carcinosarcoma
KW - PD-L1
KW - Tumor immune microenvironment
UR - https://www.scopus.com/pages/publications/85154539438
UR - https://www.scopus.com/pages/publications/85154539438#tab=citedBy
U2 - 10.1097/PGP.0000000000000890
DO - 10.1097/PGP.0000000000000890
M3 - Article
C2 - 35639400
SN - 0277-1691
VL - 42
SP - 364
EP - 375
JO - International Journal of Gynecological Pathology
JF - International Journal of Gynecological Pathology
IS - 4
ER -