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

Abstract

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.

Comprehensive Genomic Characterization of Tumor Microenvironment and Relevant Signature in Clear Cell Renal Cell Carcinoma

“…However, the powerful biomarkers are warranted for predicting the drug response of immune checkpoint inhibitors. Previous researchers found that PD-1 or PD-L1 expression levels, MSI status, and mutational load were not ideal factors for predicting the benefits of drugs with lower sensitivity ( 33 – 35 ). So far, whether TMB correlates with improved survival outcomes or promotion of immunotherapies remains controversial in ccRCC and large cohorts are needed to validate its significance ( 36 ).…”

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer

“…Clear cell RCC is the most common RCC subtype and has already been extensively analyzed for PD-L1 expression in earlier studies [ 14 , 18 – 21 , 25 , 26 , 28 , 29 , 31 , 32 , 35 , 39 , 40 , 49 , 51 ]. Our rate of 2–6% PD-L1 positive clear cell RCCs (depending on the cut-off level to define PD-L1 positivity) is in the lower range of published data with PD-L1 positivity ranging from 0 to 77% in studies analyzing 34–756 clear cell RCCs [ 14 , 18 – 21 , 25 , 26 , 28 , 29 , 31 , 32 , 35 , 39 , 40 , 49 , 51 ]. Reasons that are typically hold accountable for discrepant results in IHC studies include different antibodies, staining protocols, and criteria to define positivity.…”

“…1). These studies have described PD-L1 positivity to occur in 0–47% of clear cell RCC at a cut-off level of 1% or 5% stained cancer cells to define positivity [ 18 , 19 , 25 , 28 , 32 , 35 , 49 , 51 ]. The quantity of tissue analyzed per patient and difficulties in the distinction of interspeared PD-L1 positive macrophages that are interspersed between cancer cells from true PD-L1 positive cancer cells might also contribute to the data diversity of PD-L1 immunohistochemistry in the literature.…”

“…This was independent of the selected cut-offs and fits well with earlier data. 22 of 30 studies investigating the impact of PD-L1 expression on patient prognosis in 36–756 RCC patients have reported significantly worse outcomes in patients with PD-L1 positive tumors [ 13 , 15 , 19 , 21 – 32 , 39 , 40 , 49 – 51 , 53 ]. Both the known functions of PD-L1 and the particularly frequent PD-L1 expression in oncocytoma—the only benign tumor included in our study—argue against a direct role of PD-L1 expression for tumor progression.…”

“…PD-L1 expression—both on cancer cells and on tumor-infiltrating immune cells—predicts a favorable response to immune checkpoint inhibitors in various tumor types [ 12 ]. In RCC, several studies suggested that PD-L1 positivity is associated with a high number of tumor-infiltrating lymphocytes [ 13 – 20 ] and poor prognosis in cancers treated otherwise [ 15 , 17 , 19 , 21 – 32 ]. A minority of studies came to different conclusions [ 20 , 33 – 38 ].…”