Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma

Krabbe, Laura Maria; Heitplatz, Barbara; Preuss, Sina; Hutchinson, Ryan; Woldu, Solomon L.; Singla, Nirmish; Boegemann, Martin; Wood, Christopher G.; Karam, Jose A.; Weizer, Alon Z.; Raman, Jay D.; Remzi, Mesut; Rioux‐Leclercq, Nathalie; Haitel, Andrea; Rapoport, L.; Glybochko, Petr; Roscigno, Marco; Bolenz, Christian; Bensalah, Karim; Sagalowsky, Arthur I.; Shariat, Shahrokh F.; Lotan, Yair; Xylinas, Évanguelos; Margulis, Vitaly

doi:10.1016/j.juro.2017.06.086

Cited by 57 publications

(54 citation statements)

References 30 publications

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“…Skala et al did not detect a correlation between PD‐L1 positivity and cancer‐specific survival, while Zhang et al reported that PD‐L1 positivity on tumor cells was associated with poor cancer‐specific survival. In contrast, Krabbe et al reported that PD‐L1 positivity was associated with better outcomes among patients with high‐grade organ‐confined UTUC. There are several possible explanations for these discrepancies, such as differences in the cohorts and immunohistochemical methods (eg, antibody clones, detection systems, and positivity cutoffs).…”

Section: Discussionmentioning

confidence: 90%

“…First, the immunohistochemistry was performed using TMA slides, rather than whole‐tissue sections, which may have resulted in underestimated heterogeneity of the tumors’ PD‐L1 positivity. However, TMAs are useful for examining large numbers of samples in standardized conditions and are widely used in studies that have examined PD‐L1 positivity in various cancers . In addition, we systematically constructed the TMAs using large 2‐mm cores from the tumor's center and periphery and detected a significant correlation between PD‐L1 positivity at the two regions in the same tumor.…”

Section: Discussionmentioning

confidence: 99%

“…However, several other studies have revealed inconsistent results regarding the association between tumor PD-L1 positivity and prognosis in cases of UC. [8][9][10][11][12][13][14][15][16][17] Therefore, it is important to improve our understanding of the prognostic significance of PD-L1 expression in UC, in order to better select patients who are likely to respond to PD-1/PD-L1 blockade.…”

Section: Introductionmentioning

confidence: 99%

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The prognostic value of PD‐L1 expression in upper tract urothelial carcinoma varies according to platelet count

et al. 2018

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Programmed cell death ligand‐1 (PD‐L1) is a ligand for programmed cell death‐1 (PD‐1) that negatively regulates T‐cell activation and plays a crucial role in suppressing anti‐tumor host immunity. Although PD‐L1 is a promising immunotherapy target in various cancers, including urothelial carcinoma (UC), the prognostic significance of PD‐L1 in UC is unclear. As platelets help protect tumor cells from immune elimination in the circulatory system, we hypothesized that tumor PD‐L1 and circulating platelets might synergistically promote tumor metastasis, and that the prognostic significance of PD‐L1 might vary according to platelet count. We immunohistochemically examined tumor PD‐L1 expression in 271 patients with upper tract UC, which revealed PD‐L1 positivity in 31 of 271 cases (11%). The associations of tumor PD‐L1 expression with outcomes varied among patients with high or low platelet counts (P interaction < 0.004). Among patients with high platelet counts (N = 136), PD‐L1 positivity (N = 15) was significantly associated with shorter metastasis‐free survival (univariate hazard ratio [HR]: 6.23, 95% confidence interval [CI]: 2.95‐13.1; multivariate HR: 2.68, 95% CI: 1.27‐5.64) and shorter overall survival (univariate HR: 4.92, 95% CI: 2.14‐11.3, multivariate HR: 2.78, 95% CI: 1.19‐6.51). In contrast, among patients with low platelet counts (N = 135), PD‐L1 positivity (N = 16) was not significantly associated with these outcomes. Our results suggest that tumor PD‐L1 expression and platelet count might interact and help regulate tumor progression. Although a larger prospective study is needed to validate our findings, this relationship is important to consider, as immunotherapies targeting the PD‐1/PD‐L1 axis have gained significant attention as promising therapies for UC.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The prognostic value of PD‐L1 expression in upper tract urothelial carcinoma varies according to platelet count

et al. 2018

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“…PD‐L1 expression in TCs impairs T‐cell regulation, disrupts the antitumoral immune response, and contributes to an immunosuppressive microenvironment, allowing tumour immune escape . In several cancer types, such as HNSCC, oropharyngeal squamous cell carcinoma (SCC), pulmonary adenocarcinoma, oesophageal SCC, and urothelial carcinoma, PD‐L1 immunoexpression has been reported to be associated with advanced tumour stage, poor clinical outcome, and/or decreased overall survival. Similarly, in a cohort of 219 salivary gland carcinomas of various types, including 31 SDCs, Mukaigawa et al .…”

Section: Discussionmentioning

confidence: 99%

“…[29][30][31][32] In the present study, we investigated the immune environment in SDC, which is an an aggressive high-grade salivary malignancy, focusing on the immunoexpression of PD-L1, PD-1, the CTA PRAME, and MHC I. PD-L1 expression in TCs impairs T-cell regulation, disrupts the antitumoral immune response, and contributes to an immunosuppressive microenvironment, allowing tumour immune escape. 1,[33][34][35][36] In several cancer types, such as HNSCC, 12 oropharyngeal squamous cell carcinoma (SCC), 37 pulmonary adenocarcinoma, 38 oesophageal SCC, 39 and urothelial carcinoma, 40 PD-L1 immunoexpression has been reported to be associated with advanced tumour stage, poor clinical outcome, and/or decreased overall survival. Similarly, in a cohort of 219 salivary gland carcinomas of various types, including 31 SDCs, Mukaigawa et al reported that a high level of PD-L1 expression in TCs was associated with poor overall survival, DSS, and DFS.…”

Section: Discussionmentioning

confidence: 99%

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Jungbluth

Frosina

et al. 2019

Histopathology

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Aims Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that results in high mortality rates and is often resistant to chemotherapy. Anti‐programmed death‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) checkpoint inhibitors have led to dramatic improvements in patients with various cancers. Other immunotherapeutic approaches, e.g. cancer vaccines, have shown promising results. Cancer testis antigens, e.g. preferentially expressed antigen in melanoma (PRAME), are regarded as promising vaccine targets because of their tumour‐specific expression pattern. Methods and results We analysed the immunoexpression of PD‐L1, PD‐1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression levels of PD‐L1 in tumour cells (TCs) and immune cells (ICs), PD‐1 in ICs, PRAME in TCs and MHC I in TCs were analysed, and were correlated with outcome. PRAME expression was seen in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. With the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, the criteria being a combined positive score of ≥1, TC% ≥1%, and TC% ≥25%, 35 (66%), 17 (32%) and three cases (6%), respectively, were deemed to be positive for PD‐L1. PD‐1‐positive ICs were seen in 35 (66%) cases. MHC I down‐regulation was seen in 82% of SDCs. There was a significant correlation among PD‐L1 expression in ICs, PD‐1 expression in ICs, and PRAME expression in TCs. PD‐L1 expression in TCs and lack of PD‐1 expression in ICs were associated with decreased disease‐specific survival in SDC patients. Conclusions Alterations of the tumour immune microenvironment are common in SDCs, including expression of PD‐1/PD‐L1 and PRAME, which opens the way to potential novel immune therapies, such as cancer vaccination and PD‐1/PD‐L1 blockade, in these tumours.

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Risk Stratification of Upper Tract Urothelial Carcinoma for Kidney-Sparing Surgery

2021

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Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma

Cited by 57 publications

References 30 publications

The prognostic value of PD‐L1 expression in upper tract urothelial carcinoma varies according to platelet count

The prognostic value of PD‐L1 expression in upper tract urothelial carcinoma varies according to platelet count

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Risk Stratification of Upper Tract Urothelial Carcinoma for Kidney-Sparing Surgery

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