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

Abstract

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.

Prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in uterine carcinosarcoma

“…Although it was shown that PD-L1 expression was related with worse prognosis in tumors such as melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), prostate cancer, and colorectal cancer, we found that PD-L1 expression was associated with better prognosis in UCS [5,6]. Similar to our study PDL-1 positivity has been found to be associated with good prognosis in ovarian carcinosarcoma [10]. By this time the prognostic effect of PD-L1 expression in ovarian cancer is controversial.…”

“…Zu at al. revealed the negative impact of the mesenchymal PD-1 expression on survival [10]. Paydas at al.…”

Prognostic significance of programmed cell death ligand 1 expression in patients with ovarian carcinoma

“…[ 20 ] Three comparisons included patients diagnosed with epithelial ovarian carcinoma (EOC), whereas remaining comparisons included patients with the subtypes of EOC: 8 comparisons included patients with HGSOC, 2 comparisons included patients with OCCC, 1 comparison included patients with ovarian carcinosarcoma (OCS). The HR with 95% CI was calculated according to the methods provided by Tierney et al in the study by Zhu et al [ 25 ] The studies by Hamanishi et al and by Xu et al provided the relative risk (RR) with 95% CI from Cox multifactor regression analysis using Cox hazard model, which were pooled with HRs together in this meta-analysis.…”

Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms

“…Therefore, it is essential to fully understand PD-L1 expression in NSCLC and the relationship between PD-L1 expression and prognosis. PD-L1 expression has been found in several cancers, including breast cancer 9 , lung cancer 10 , gastric cancer 11 , colorectal cancer 12 , ovarian cancer 13 , and prostate cancer 14 . Our previous study showed that positive PD-L1 expression was associated with poor prognosis in gastric cancer 15 , breast cancer 16 and surgical lung squamous cell carcinoma 17 .…”