Prevalence and Prognostic Implications of PD-L1 Expression in Soft Tissue Sarcomas

Kelany, Mohamed; Barth, Thomas F.E.; Salem, Dina; Shakweer, Marwa M

doi:10.3389/pore.2021.1609804

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…In sarcomas, PD-L1 expression levels have shown conflicting association with ICI response [ 78 ]. Indeed, levels of PD-L1 expression can vary widely between different histological subtypes [ 79 ] (Fig. 2 ) that is further complicated by the heterogenous TME present in primary and metastatic lesions [ 78 , 80 ].…”

Section: Biomarkers Approved For Immune Checkpoint Inhibition In Cancermentioning

confidence: 99%

Biomarkers for immune checkpoint inhibition in sarcomas – are we close to clinical implementation?

Yiong,

Lin,

Lim

et al. 2023

Biomark Res

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Sarcomas are a group of diverse and complex cancers of mesenchymal origin that remains poorly understood. Recent developments in cancer immunotherapy have demonstrated a potential for better outcomes with immune checkpoint inhibition in some sarcomas compared to conventional chemotherapy. Immune checkpoint inhibitors (ICIs) are key agents in cancer immunotherapy, demonstrating improved outcomes in many tumor types. However, most patients with sarcoma do not benefit from treatment, highlighting the need for identification and development of predictive biomarkers for response to ICIs. In this review, we first discuss United States (US) Food and Drug Administration (FDA)-approved and European Medicines Agency (EMA)-approved biomarkers, as well as the limitations of their use in sarcomas. We then review eight potential predictive biomarkers and rationalize their utility in sarcomas. These include gene expression signatures (GES), circulating neutrophil-to-lymphocyte ratio (NLR), indoleamine 2,3-dioxygenase (IDO), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and mucin domain-containing protein 3 (TIM-3), TP53 mutation status, B cells, and tertiary lymphoid structures (TLS). Finally, we discuss the potential for TLS as both a predictive and prognostic biomarker for ICI response in sarcomas to be implemented in the clinic.

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Section: Biomarkers Approved For Immune Checkpoint Inhibition In Cancermentioning

confidence: 99%

Biomarkers for immune checkpoint inhibition in sarcomas – are we close to clinical implementation?

Yiong,

Lin,

Lim

et al. 2023

Biomark Res

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“…While it is generally believed that STS have low immune cell infiltration, this is not entirely accurate for all STS subtypes and patients (Petitprez et al 2020 ; Toulmonde et al 2020 ). Although immune checkpoint molecules have been detected in various STS (Kelany et al 2021 ; Klaver et al 2020 ; Orth et al 2020 ), clinical trials of these targets have not shown promising results (Banks & D’Angelo 2022 ). The objective response rate in patients with STS following treatment with the combination of nivolumab (anti-PD-1 antibody) and ipilimumab (anti-CTLA-4 antibody) was found to be 16%, which was similar to the response rate obtained with the conventional chemotherapy drug doxorubicin (overall response rate of 14%) (D’Angelo et al 2018 ; Judson et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive analysis of CD47 expression in various histological subtypes of soft tissue sarcoma: exploring novel opportunities for macrophage-directed treatments

Benesova,

Capkova,

Ozaniak

et al. 2024

J Cancer Res Clin Oncol

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Purpose The CD47 molecule, often referred to as the “do not eat me” signal, is frequently overexpressed in tumor cells. This signaling pathway limits phagocytosis by macrophages. Our objective was to determine CD47 abundance in various soft tissue sarcomas (STS) to investigate whether it could serve as a potential evasion mechanism for tumor cells. Additionally, we aimed to assess the prognostic value of CD47 expression by examining its association with different clinicopathological factors. This study aimed to elucidate the significance of CD47 in the context of emerging anti-tumor targeting approaches. Methods In this retrospective study, formalin-fixed paraffine-embedded (FFPE) tumor tissues of 55 treatment-naïve patients were evaluated by immunohistochemistry for the abundance of CD47 molecule on tumor cells. The categorization of CD47 positivity was as follows: 0 (no staining of tumor cells), 1 + (less than 1/3 of tumor area positive), 2 + (between 1/3 and 2/3 of tumor area positive), and 3 + (more than 2/3 of tumor area positive for CD47). Next, we compared CD47 abundance between different tumor grades (G1–3). We used Kaplan–Meier survival curves with log-rank test to analyze the differences in survival between patients with different CD47 expression. Moreover, we performed Cox proportional hazards regression model to evaluate the clinical significance of CD47. Results CD47 is widely prevalent across distinct STS subtypes. More than 80% of high grade undifferentiated pleiomorphic sarcoma (UPS), 70% of myxofibrosarcoma (MFS) and more than 60% of liposarcoma (LPS) samples displayed a pattern of moderate-to-diffuse positivity. This phenomenon remains consistent regardless of the tumor grade. However, there was a tendency for higher CD47 expression levels in the G3 group compared to the combined G1 + G2 groups when all LPS, MFS, and UPS were analyzed together. No significant associations were observed between CD47 abundance, death, and metastatic status. Additionally, high CD47 expression was associated with a statistically significant increase in progression-free survival in the studied cohort of patients. Conclusion This study highlights the potential of the CD47 molecule as a promising immunotherapeutic target in STS, particularly given its elevated expression levels in diverse sarcoma types. Our data showed a notable trend linking CD47 expression to tumor grade, while also suggesting an interesting correlation between enhanced abundance of CD47 expression and a reduced hazard risk of disease progression. Although these findings shed light on different roles of CD47 in STS, further research is crucial to assess its potential in clinical settings.

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“…The presence of PD-L1 expression may also have important prognostic consequences. [9][10][11][12] There are numerous studies on PD-L1 expression in malignant epithelial neoplasms, but less data are available on its utility in soft tissue sarcomas.…”

Section: Introductionmentioning

confidence: 99%

Expression of PD-L1 in malignant soft tissue neoplasm and their correlation with clinicopathological parameters

Mishra

Singh

Kumar

et al. 2023

JLP

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Objectives Programmed death ligand-1 (PD-L1) expression in malignant epithelial neoplasms has been the subject of numerous studies; however, less data on its application to sarcomas are available. This research focused on the expression of PD-L1 and how it correlated with clinicopathological characteristics in soft tissue sarcomas. Materials and Methods The anti-PD-L1 antibody and Ki-67 were stained in 50 cases of sarcoma that had been confirmed by biopsy and immunohistochemistry. The tumor cell percentage with complete or incomplete membrane staining was calculated. Sarcomas were categorized as positive (>1% of tumor cells with complete or incomplete membrane staining) or negative (≤1% of tumor cells with complete or incomplete membrane staining). The data were analyzed using statistical package for Social Sciences version 21.0. Results The soft tissue sarcomas showing marked pleomorphic morphology were significantly linked to positive PD-L1 expression than other subtypes of sarcomas (p = 0.042). Proliferation index grade III accounts for 62.5% of cases with positive PD-L1 expression, followed by proliferation index grade II with 25% cases and grade I with 12.5% cases. On comparing statistically, this difference was found to be significant (p = 0.013). A significant association was found between PD-L1 expression and the poor outcome of follow-up (p = 0.024). Conclusion Our study showed a significant relationship between malignant soft tissue tumor positivity for PD-L1 and pleomorphic morphology, a higher proliferation index grade, and a poorer prognosis.

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Prevalence and Prognostic Implications of PD-L1 Expression in Soft Tissue Sarcomas

Cited by 10 publications

References 19 publications

Biomarkers for immune checkpoint inhibition in sarcomas – are we close to clinical implementation?

Biomarkers for immune checkpoint inhibition in sarcomas – are we close to clinical implementation?

A comprehensive analysis of CD47 expression in various histological subtypes of soft tissue sarcoma: exploring novel opportunities for macrophage-directed treatments

Expression of PD-L1 in malignant soft tissue neoplasm and their correlation with clinicopathological parameters

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