PD-L1 and PD-1 expression correlate with prognosis in extrahepatic cholangiocarcinoma

Ma, Ke; Wei, Xin; Dong, Diansheng; Wu, Yinying; Geng, Qing; Li, Enxiao

doi:10.3892/ol.2017.6105

Cited by 55 publications

(64 citation statements)

References 41 publications

(57 reference statements)

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“…In this clinical trial, PD‐L1 positivity was defined as staining in 1% of cells in tumour nests or PD‐L1‐positive bands in the stroma as determined with the 22C3 assay . However, data regarding PD‐L1 expression status in extrahepatic biliary tract cancers are still limited, and the frequency of PD‐L1 expression in bile duct cancer has varied among studies (Table ) . This variability may be explained by multiple factors, including assay method, interpretation method, specimen type (biopsy; surgically resected specimen), and patient demographics (including tumour stage) …”

Section: Discussionmentioning

confidence: 99%

“…4 However, data regarding PD-L1 expression status in extrahepatic biliary tract cancers are still limited, and the frequency of PD-L1 expression in bile duct cancer has varied among studies (Table 1). [13][14][15][16] This variability may be explained by multiple factors, including assay method, interpretation method, specimen type (biopsy; surgically resected specimen), and patient demographics (including tumour stage). 18,22 Regarding the PD-L1 detection method, currently available tests for PD-L1 expression include commercial assays for clinical trials (22C3, SP263, and SP142), and antibodies labelled as being for research use only (laboratory-developed tests), most commonly the E1L3N antibody.…”

Section: Discussionmentioning

confidence: 99%

“…12 So far, only four studies have investigated PD-L1 expression in bile duct cancers. The reported frequency of PD-L1 positivity has varied, ranging from 9.1% to 72.2%, [13][14][15][16] and all studies used laboratorydeveloped tests, including the E1L3N assay (Table 1). PD-L1 expression in tumour cells has also been associated with an unfavourable clinical outcome in some studies.…”

Section: Introductionmentioning

confidence: 99%

“…PD-L1 expression in tumour cells has also been associated with an unfavourable clinical outcome in some studies. 15,16 Herein, we evaluated PD-L1 expression in 183 extrahepatic bile duct cancers, including 89 perihilar and 94 distal bile duct cancers. PD-L1 expression was evaluated with the 22C3, SP263 and E1L3N assays, and the results were compared.…”

Section: Introductionmentioning

confidence: 99%

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Programmed cell death ligand‐1 (PD‐L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti‐PD‐L1 antibodies

et al. 2019

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Aims Pembrolizumab has shown promising results for patients with programmed cell death ligand‐1 (PD‐L1)‐positive advanced biliary tract cancer in an ongoing clinical trial. However, data on PD‐L1 expression in bile duct cancers is limited, and the frequency of PD‐L1 positivity varies, which may be partly due to the assay used. The aim of this study was to evaluate PD‐L1 expression status in bile duct cancers by using 22C3, SP263 and E1L3N antibodies. Methods and results We evaluated PD‐L1 expression in tissue microarrays of 183 extrahepatic bile duct cancers, including 89 perihilar and 94 distal bile duct cancers, by using 22C3, SP263 and E1L3N. When the 22C3 assay was used, tumoral PD‐L1 was shown to be expressed in 16.9% of cases at a 1% threshold. When the SP263 and E1L3N assays were used, tumoral PD‐L1 was shown to be expressed in 26% and 7.1% of cases, respectively. When whole tissue sections were examined, 59.6% of PD‐L1‐positive cases showed a low percentage (<10%) of positive tumour cells. Tumoral PD‐L1 positivity was associated with poor histological differentiation (P = 0.017) and the biliary epithelial phenotype (P = 0.041). High tumoral PD‐L1 expression (≥10%) was associated with worse overall survival (OS) and disease‐free survival (DFS) (OS, P = 0.012; DFS, P = 0.042). Conclusions PD‐L1 was expressed in a small subset of patients with bile duct cancer, and the percentage of positive tumour cells was low in PD‐L1‐positive cases. The SP263 assay showed the highest PD‐L1 positivity in both tumour cells and immune cells, followed by the 22C3 and E1L3N assays. High PD‐L1 expression was associated with a poor prognosis in extrahepatic bile duct cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Programmed cell death ligand‐1 (PD‐L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti‐PD‐L1 antibodies

et al. 2019

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“…High expression of PD‐L1 among other immune checkpoints and of tumour‐specific neoantigens characterized a subset of CCA patients (5.9%, 14/239) with high mutational load and poor prognosis . Both PD‐1 and PD‐L1 are up‐regulated in neoplastic cells, and overexpression is associated with increased invasiveness, poor outcome, and worse disease‐ and metastasis‐free survival, especially when accompanied by low CD3 + or CD8 + infiltrate . Conversely, low PD‐L1 expression (in combination with high MHC‐I expression) was found to be related to favourable prognosis .…”

Section: Mechanisms Of Immune Surveillance and Immune Escapementioning

confidence: 99%

The tumour microenvironment and immune milieu of cholangiocarcinoma

Fabris

Perugorria

Mertens

et al. 2019

Liver International

131

124

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Tumour microenvironment is a complex, multicellular functional compartment that, particularly when assembled as an abundant desmoplastic reaction, may profoundly affect the proliferative and invasive abilities of epithelial cancer cells. Tumour microenvironment comprises not only stromal cells, mainly cancer‐associated fibroblasts, but also immune cells of both the innate and adaptive system (tumour‐associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes), and endothelial cells. This results in an intricate web of mutual communications regulated by an extensively remodelled extracellular matrix, where the tumour cells are centrally engaged. In this regard, cholangiocarcinoma, in particular the intrahepatic variant, has become the focus of mounting interest in the last years, largely because of the lack of effective therapies despite its rising incidence and high mortality rates worldwide. On the other hand, recent studies in pancreatic cancer, which similarly to cholangiocarcinoma, is highly desmoplastic, have argued against a tumour‐promoting function of the tumour microenvironment. In this review, we will discuss recent developments concerning the role of each cellular population and their multifaceted interplay with the malignant biliary epithelial counterpart. We ultimately hope to provide the working knowledge on how their manipulation may lead to a therapeutic gain in cholangiocarcinoma.

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A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer

et al. 2020

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IMPORTANCE Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1-expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC.OBJECTIVE To evaluate anticancer activity of nivolumab in patients with advanced refractory BTC. DESIGN, SETTING, AND PARTICIPANTSIn this single-group, multicenter phase 2 study of nivolumab, 54 patients with histologically confirmed BTC whose disease progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy were enrolled between October 5, 2016, and December 26, 2018. Analysis was performed on an intention-to-treat basis.INTERVENTIONS Nivolumab, 240 mg, was delivered intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred. MAIN OUTCOMES AND MEASURESThe primary end point was investigator-assessed objective response rate, and the secondary end points were progression-free survival, overall survival, and incidence of adverse events.RESULTS A total of 54 patients (27 men and 27 women; median age, 65 years [range, 28-86 years]) enrolled, and 46 (22 men and 24 women; median age, 65 years [range, 28-86 years]) were examined for objective response with radiologic imaging. The investigator-assessed objective response rate was 22% (10 of 46), including 1 unconfirmed partial response, with a disease control rate of 59% (27 of 46). Central independent review found an objective response rate of 11% (5 of 46), including 1 unconfirmed partial response, with a disease control rate of 50% (23 of 46). All patients who responded to treated (hereafter referred to as responders) had mismatch repair protein-proficient tumors. The median duration of investigator-assessed response was not reached, with a median follow-up of 12.4 months. Among the intention-to-treat population, median progression-free survival was 3.68 months (95% CI, 2.30-5.69 months) and median overall survival was 14.24 months (95% CI, 5.98 months to not reached). Programmed cell death 1 ligand 1 expression in tumors was associated with prolonged progression-free survival (hazard ratio, 0.23; 95% CI, 0.10-0.51; P < .001). The most common treatment-related grade 3 or 4 toxic effects were hyponatremia (3 of 54 [6%]) and increased alkaline phosphatase (2 of 54 [4%]).CONCLUSIONS AND RELEVANCE This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients.

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PD-L1 and PD-1 expression correlate with prognosis in extrahepatic cholangiocarcinoma

Cited by 55 publications

References 41 publications

Programmed cell death ligand‐1 (PD‐L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti‐PD‐L1 antibodies

Programmed cell death ligand‐1 (PD‐L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti‐PD‐L1 antibodies

The tumour microenvironment and immune milieu of cholangiocarcinoma

A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer

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