Clinical Significance of Programmed Death Ligand‑1 and Intra-Tumoral CD8⁺ T Lymphocytes in Ovarian Carcinosarcoma

<div><p>Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients’ clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS.</p></div

Three-year survival rate of 19 OCS patients according to clinicopathologic characteristics and tumor CD8+ T lymphocytes (Log-rank).

<p>Three-year survival rate of 19 OCS patients according to clinicopathologic characteristics and tumor CD8+ T lymphocytes (Log-rank).</p

Kaplan-Meier survival curves of patients with ovarian carcinosarcoma (OCS).

<p>Fig 1A and 1B show the post-operative survival classified according to tumor site (unilateral tumor vs. bilateral tumors) and residual disease (no visible disease vs. visible residual disease), respectively. Patients with bilateral tumors and visible residual disease showed significantly worse prognosis (p = 0.019 and p = 0.027, log-rank test). Fig 1C and 1D show the post operation survival curves between mesenchymal PD-L1-positive and PD-L1-negative expression. Intraepithelial PD-L1-positive patients had a trend of better survival than PD-L1-negative patients (p = 0.061). A significant difference in postoperative prognosis between mesenchymal PD-L1-positive and PD-L1-negative patients was observed (p = 0.036).</p

Demographic and clinicopathological characteristics of 19 OCS patients.

<p>Demographic and clinicopathological characteristics of 19 OCS patients.</p

Immunohistochemical staining for programmed death ligand 1 (PD-L1) in intraepithelial and mesenchymal tumor tissue.

<p>A-C: Haematoxylin and eosin-prepared samples of OCS tissues containing both carcinomatous (☆) and mesenchymal components (ϒ). The homologous subtype is composed of high-grade undifferentiated round cell or spindle cell sarcomatous proliferation (tissue native to the ovary, △). Heterologous carcinosarcoma may show cartilaginous differentiation (tissue not native to the ovary, arrow). D-F: Representative immunohistochemical staining for PD-L1 expression in OCS. Samples were divided into three groups according to the intensity of PD-L1 expression: weak (D), moderate (E), and strong (F) staining of PD-L1. Tissue of placenta (G) was used as positive control for PD-L1 expression (at x400 magnification).</p

Correlation between tumor PD-L1 expression and intratumoral CD8+ T lymphocyte count.

<p>Correlation between tumor PD-L1 expression and intratumoral CD8+ T lymphocyte count.</p

Correlations between the expression of PD-Ls or tumor-infiltrating CD8+ lyphocytes and clinicopathological characteristics in ovarian carcinosarcoma (<i>n</i> = 19).

<p>Correlations between the expression of PD-Ls or tumor-infiltrating CD8+ lyphocytes and clinicopathological characteristics in ovarian carcinosarcoma (<i>n</i> = 19).</p

Three-year survival rate of 19 OCS patients according to clinicopathologic characteristics and tumor PD-L1 status (Log-rank).

<p>Three-year survival rate of 19 OCS patients according to clinicopathologic characteristics and tumor PD-L1 status (Log-rank).</p