Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein–Barr virus-associated gastric cancer

Abstract

Background:This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein–Barr virus-associated gastric cancer (EBVaGC).Methods:After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively analysed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour stroma area (str-).Results:Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell PD-L1 positivity was found to be significantly associated with lymph node (LN) metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028). Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an improved DFS, although not significant (P=0.060 and P=0.073, respectively).Conclusions:Intraepithelial tumour cells PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.

Integrative analysis of PD‐L1 DNA status, mRNA status and protein status, and their clinicopathological correlation, in diffuse large B‐cell lymphoma

“…The programmed cell death protein1 (PD-1)-programmed death-ligand 1 (PD-L1) signalling pathway plays an important inhibitory role in the immune system, and its abnormal expression has been reported in a series of tumours, such as gastric cancer, non-small-cell lung carcinoma (NSCLC), and Hodgkin lymphoma. [4][5][6] PD-L1 has been considered to be a key factor in lymphocyte inhibition and immune response termination. 7 Studies have demonstrated that PD-L1 is up-regulated and results in a poorer prognosis in some types of cancer, including ovarian cancer, oesophageal cancer, and hepatocellular cancer.…”

Transcriptional analysis of immune genes in Epstein–Barr virus-associated gastric cancer and association with clinical outcomes

“…Previous EBVaGC-specific studies have focused on histomorphological characteristics, such as tumor-infiltrating lymphocyte (TIL) patterns [4] or expression of PD-L1 through immunohistochemistry (IHC) Raghav Sundar and Aditi Qamra have contributed equally and shared the first authorship. [5,6]. Large genomic studies of gastric cancer conducted by The Cancer Genome Atlas group (TCGA) [1] and the Asian Cancer Research Group (ACRG) [7] only include a small sample size of EBVaGC.…”

Immunohistochemical characteristics of bladder cancer in patients with virus-positive tumors

“…Однако требуется продолжение исследования. В целом роль экспрессии данного маркера в течении и прогнозе опухолевых заболеваний различных локализаций активно обсуждается в литературе [33][34][35], однако все сходятся во мнении, что при ВЭБ-ассоциированных неоплазмах экспрессия PD-L1 повышается [34,36]. Таким образом, по мере развития опухолевого процесса экспрессия факторов ангиогенеза увеличивается у этой категории больных.…”