PD-L1 expression in papillary renal cell carcinoma

Motoshima, Takanobu; Komohara, Yoshihiro; Ma, Chaoya; Dewi, Arni Kusuma; Noguchi, Hirotsugu; Yamada, Sohsuke; Nakayama, Toshiyuki; Kitada, Shohei; Kawano, Yoshiaki; Takahashi, Wataru; Sugimoto, Masahiro; Takeya, Motohiro; Fujimoto, Naohiro; Oda, Yoshinao; Eto, Masatoshi

doi:10.1186/s12894-016-0195-x

Cited by 42 publications

(21 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For PD‐L2 staining, anti‐PD‐L2 antibody (clone D7U8C; Cell Signaling Technology, Danvers, MA, USA) was used as the primary antibody. The specificity of the anti‐PD‐L2 antibody has been tested previously . Horseradish peroxidase (HRP)‐labeled anti‐rabbit immunoglobulin antibody (Nichirei, Tokyo, Japan) was used as the secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

Self Cite

View full text Add to dashboard Cite

The percentage of programmed death ligand 1 (PD‐L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer. PD‐L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD‐L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD‐L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD‐L1 expression was negative in 169 patients (73.2%), 1%‐49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD‐L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD‐L1 expression was associated with high‐grade cancer cells and in higher stage cancer. PD‐L2 was negative in 109 patients (47.2%), 1%‐49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD‐L2‐positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty‐five patients (15.2%) were positive for both PD‐L1 and PD‐L2, whereas 81 patients (35.1%) were negative for both PD‐L1 and PD‐L2. Log‐rank analysis showed that progression‐free survival and overall survival were significantly the longest in the PD‐L1‐negative and PD‐L2‐positive groups (P < .0001 and P = .0120). We observed lower PD‐L1 or PD‐L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD‐L1 or PD‐L2 expression specifically in cancer cells.

show abstract

Section: Methodsmentioning

confidence: 99%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Exosomal microRNAs (miRNAs), which are transferred by EVs, are promising and reliable tools for cancer diagnosis and clinical application [18]. PD-L1 overexpression has been examined as a prognostic factor in diverse cancers including lung cancer [19], gastric cancer [20], ovarian cancer [21], breast cancer [22], prostate cancer [23], bladder cancer [24], cervical cancer [25], cholangiocarcinoma [26], colorectal cancer [27], nasopharyngeal carcinoma [28], diffuse large B-cell lymphoma [29], pancreatic cancer [30], soft-tissue sarcoma [31], renal cell carcinoma [32], and head and neck squamous cell carcinoma [33]. In addition, in patients with melanoma, exosomal PD-L1 is an indicator of immune activation early after the initiation of treatment with immune checkpoint inhibitors (ICIs) and is associated with clinical response to ICIs [34].…”

Section: Introductionmentioning

confidence: 99%

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

Yang

Shui

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a metaanalysis to identify the prognostic role of PD-L1 in melanoma. Methods: A thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg's test and Egger's test. Results: Thirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57-1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43-1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22-0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90-1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51-1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06-4.83, P = 0.592). Conclusions: This meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

show abstract

“…However, except for the immunotherapy treated RCC showing controversial conclusions, the majority of big studies have demonstrated that PD-L1 expression is associated with a poor prognosis in RCC, presumably due to its immunosuppressive function 13 15–25. Many of these previous studies performed immunohistochemistry using antibodies not currently available in the market, including the laboratory-derived antibody 5H1 and the pharmaceutical trial antibody 28–8 13 15–25. Two studies adopted commercially available PD-L1 antibody E1L3N, both in the Asian cohort 21 23.…”

Section: Introductionmentioning

confidence: 99%

“…Many of these previous studies performed immunohistochemistry using antibodies not currently available in the market, including the laboratory-derived antibody 5H1 and the pharmaceutical trial antibody 28–8 13 15–25. Two studies adopted commercially available PD-L1 antibody E1L3N, both in the Asian cohort 21 23. As a result, there remains an urgent need to investigate PD-L1 expression in RCCs using a more commonly adopted and widely available antibody clone to make the test accessible to the majority of the laboratories and hospitals globally.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 expression is an unfavourable prognostic indicator in Asian renal cell carcinomas

et al. 2020

View full text Add to dashboard Cite

Background/aimsThe programmed cell death receptor 1 (PD-1) checkpoint inhibitor, nivolumab, has been approved for the treatment of metastatic renal cell carcinoma (RCC). However, the understanding of the expression and distribution of PD ligand 1 (PD-L1) in the tumour immune microenvironment and its prognostic role in an Asian cohort is limited. Our group investigated PD-L1 protein expression in a cohort of Asian patients with RCC of mixed ethnicity, using two commercially available antibody clones.MethodsE1L3N and SP263 anti-PD-L1 clones were used to categorise RCCs of various histological subtypes, diagnosed at our institution between 1995 and 2008, into PD-L1-positive or PD-L1-negative groups, based on a 1% Tumour Proportion Score (TPS) cut-off.ResultsIn total, 267 (83%) clear cell (cc)RCC and 55 (17%) non-ccRCC cases were studied. Overall PD-L1 protein expression rates for the entire cohort were 13% and 8% for the E1L3N and SP263 clones, respectively. Patients bearing PD-L1-positive tumours experienced significantly decreased disease-free survival (DFS; E1L3N: p=0.01; SP263: p=0.03) but not overall survival, compared with those with PD-L1-negative tumours. Multivariate survival analysis further confirmed the results of the E1L3N clone (HR 1.85, 95% CI 1.10 to 3.13, p=0.02), but not SP263, after adjusting for pathological stage, histological subtype and grade. The addition of PD-L1 (E1L3N) TPS to clinicopathological features significantly increased the prognostic value for DFS (∆LRχ2=5.25; p=0.022), compared with clinicopathological features alone.ConclusionsPD-L1 protein expression was associated with an unfavourable prognosis in our study cohort. PD-L1 (E1L3N) expression was an independent prognostic indicator of clinical outcome in all RCCs when using a 1% cut-off.

show abstract

PD-L1 expression in papillary renal cell carcinoma

Cited by 42 publications

References 28 publications

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

PD-L1 expression is an unfavourable prognostic indicator in Asian renal cell carcinomas

Contact Info

Product

Resources

About