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

Date Published: January 26, 2017

Publisher: Public Library of Science

Author(s): Jun Zhu, Hao Wen, Xingzhu Ju, Rui Bi, Wenjia Zuo, Xiaohua Wu, Viji Shridhar.

http://doi.org/10.1371/journal.pone.0170879

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.

Partial Text

Ovarian carcinosarcoma (OCS), also referred to as ovarian mixed Müllerian tumor, is a rare but aggressive malignancy, occurring in only 1% to 3% of all ovarian cancers [1]. OCS is histologically composed of malignant epithelial and mesenchymal components and classified according to the homologous or heterologous derivation of the mesenchymal tissue in their stromal element. Compared with other ovarian carcinoma, OCS displays an aggressive clinical behavior resulting in poorer survival for both local and distant disease. Moreover, the prognosis of OCS is worse than that of high-grade ovarian carcinomas with a similar stage [2]. Given the rarity and pathological diversity, there is no standard treatment modality for OCS at present. Maximal cytoreduction is still the mainstay therapy for this tumor. In the absence of randomized data, chemotherapy options for patients with OCS are based primarily on data from other ovarian and sarcoma subtypes, as well as retrospective data. Several studies have compared the outcomes between patients treated with platinum-taxane combinations and ifosfamide-based regimens, however, the results remained controversial [3–6]. Nevertheless, the response rates and clinical benefit of adjuvant chemotherapy remains inferior to that of epithelial ovarian carcinoma. Accordingly, there is a pressing effort to optimize the outcome of this generally poor-prognosis cancer by exploring molecular biomarkers that can provide accurate prognosis and targeted therapy.

Carcinosarcoma of gynecologic origin is a rare but aggressive tumor, characterized by an admixture of epithelial and mesenchymal elements. Although surgical debulking followed by adjuvant chemotherapy remains the mainstay of treatment for ovarian carcinosarcoma, low response rates and high recurrence rate is a major concern for the majority of patients [2]. Moreover, the five-year survival rate for OCS is 26.63% compared to 43.61% for serous carcinomas [17]. Cancer immunotherapy is now rapidly evolving with clinical benefits targeting the PD-1/PD-L1 pathways. Blocking of PD-L1 with monoclonal antibodies could trigger anti-tumor immune responses. It has been suggested that tumoral PD-L1 expression may be an adequate biomarker to predict immunotherapeutic responsiveness in many solid tumors. In this study we successfully revealed a negative correlation between mesenchymal CD8+ T lymphocytes and PD-L1 expression. Meanwhile, the prognostic value of CD8+ T lymphocytes and PD-L1 expression were particularly remarkable in mesenchymal component in OCS.

 

Source:

http://doi.org/10.1371/journal.pone.0170879

 

0 0 vote
Article Rating
Subscribe
Notify of
guest
0 Comments
Inline Feedbacks
View all comments