Clinical and Prognostic Value of Antigen-Presenting Cells with PD-L1/PD-L2 Expression in Ovarian Cancer Patients

Pawłowska, Anna; Kwiatkowska, Agnieszka; Suszczyk, Dorota; Chudzik, Agata; Tarkowski, Rafał; Barczyński, Bartłomiej; Kotarski, Jan; Wertel, Iwona

doi:10.3390/ijms222111563

Cited by 20 publications

(16 citation statements)

References 71 publications

(97 reference statements)

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“…In general, elevated sPD-L1 in cancer patients is indicative of poor prognosis or resistance to treatment ( 83 – 85 ). High sPD-L1 levels before neoadjuvant chemoradiotherapy (CRT) were found to be associated with younger age, and significantly increased sPD-L1 levels after CRT were associated with lymphovascular infiltration and shorter disease-free survival (DFS) ( 80 ).…”

Section: Clinical Importance Of Spd-1 and Spd-l1 In Cancermentioning

confidence: 99%

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Niu

Liu

et al. 2022

Front. Immunol.

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The immune checkpoint pathway consisting of the cell membrane-bound molecule programmed death protein 1 (PD-1) and its ligand PD-L1 has been found to mediate negative regulatory signals that effectively inhibit T-cell proliferation and function and impair antitumor immune responses. Considerable evidence suggests that the PD-1/PD-L1 pathway is responsible for tumor immune tolerance and immune escape. Blockage of this pathway has been found to reverse T lymphocyte depletion and restore antitumor immunity. Antagonists targeting this pathway have shown significant clinical activity in specific cancer types. Although originally identified as membrane-type molecules, several other forms of PD-1/PD-L1 have been detected in the blood of cancer patients, including soluble PD-1/PD-L1 (sPD-1/sPD-L1) and exosomal PD-L1 (exoPD-L1), increasing the composition and functional complications of the PD-1/PD-L1 signaling pathway. For example, sPD-1 has been shown to block the PD-1/PD-L immunosuppressive pathway by binding to PD-L1 and PD-L2, whereas the role of sPD-L1 and its mechanism of action in cancer remain unclear. In addition, many studies have investigated the roles of exoPD-L1 in immunosuppression, as a biomarker for tumor progression and as a predictive biomarker for response to immunotherapy. This review describes the molecular mechanisms underlying the generation of sPD-1/sPD-L1 and exoPD-L1, along with their biological activities and methods of detection. In addition, this review discusses the clinical importance of sPD-1/sPD-L1 and exoPD-L1 in cancer, including their predictive and prognostic roles and the effects of treatments that target these molecules.

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Section: Clinical Importance Of Spd-1 and Spd-l1 In Cancermentioning

confidence: 99%

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Niu

Liu

et al. 2022

Front. Immunol.

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“…However, previous studies described the weak response by PD-L1 inhibitors for these patients. Different components of the EOC microenvironment contribute to this failure [31]. Significant heterogeneity in EOC could be an additional factor for this inadequate response.…”

Section: Discussionmentioning

confidence: 99%

“…Significant heterogeneity in EOC could be an additional factor for this inadequate response. In HGSC at least four genomic classes were identified differing for immunoreactivity [31,32]. Therefore, a comprehensive analysis of the genomic status of EOC and immunological characteristics in the tumor microenvironment could be predictive factors for immune therapy response [2,32].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate

Jovanović¹,

Janković

Ćirković

et al. 2021

Medicina

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Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

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“…Higher PD-L1 expression (combined positive score > 10) was also predictive of a better response to pembrolizumab therapy in ovarian cancer (Matulonis et al 2019 ). Nevertheless, the cut-off value, which may be used in ovarian cancer, is still under investigation (Pawłowska et al 2021 ; Wang 2019 ). In advanced or recurrent endometrial cancer, the susceptibility to anti-PD1 therapy is determined based on hallmarks of microsatellite instability (Oaknin et al 2020 ).…”

Section: Checkpoint Blockadementioning

confidence: 99%

Immunotherapy in Ovarian Cancer

Siminiak

Czepczyński

Zaborowski

et al. 2022

Arch. Immunol. Ther. Exp.

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Despite advances in surgery and chemotherapy, ovarian cancer remains one of the most lethal malignancies. Hence, the implementation of novel treatment approaches is required to improve the outcomes of the disease. Immunotherapy has been proven to be effective in many tumors and has already been incorporated into clinical practice. In this review, we describe key strategies in immunotherapy of ovarian cancer and summarize data from clinical studies assessing immunological prospects which could improve ovarian cancer treatment approaches in the future. The most notable current strategies include checkpoint blockade agents, the use of vaccines, adoptive cell transfer, as well as various combinations of these methods. While several of these options are promising, large controlled randomized studies are still needed to implement new immunotherapeutic options into clinical practice.

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Clinical and Prognostic Value of Antigen-Presenting Cells with PD-L1/PD-L2 Expression in Ovarian Cancer Patients

Cited by 20 publications

References 71 publications

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

Biological Characteristics and Clinical Significance of Soluble PD-1/PD-L1 and Exosomal PD-L1 in Cancer

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate

Immunotherapy in Ovarian Cancer

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