Abstract
Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in pancreatic ductal adenocarcinoma (PDAC). We undertook a systematic review and meta‐analysis of immune cell infiltration, measured by immunohistochemistry (IHC), as a prognostic biomarker in PDAC. All other IHC prognostic biomarkers in PDAC were also summarised. MEDLINE, EMBASE and Web of Science were searched between 1998 and 2018. Studies investigating IHC biomarkers and prognosis in PDAC were included. REMARK score and Newcastle–Ottawa scale were used for qualitative analysis. Random‐effects meta‐analyses were used to pool results, where possible. Twenty‐six articles studied immune cell infiltration IHC biomarkers and PDAC prognosis. Meta‐analysis found high infiltration with CD4 (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.51–0.83.) and CD8 (HR = 0.68, 95% CI = 0.55–0.84.) T‐lymphocytes associated with better disease‐free survival. Reduced overall survival was associated with high CD163 (HR = 1.62, 95% CI = 1.03–2.56). Infiltration of CD3, CD20, FoxP3 and CD68 cells, and PD‐L1 expression was not prognostic. In total, 708 prognostic biomarkers were identified in 1101 studies. In summary, high CD4 and CD8 infiltration are associated with better disease‐free survival in PDAC. Increased CD163 is adversely prognostic. Despite the publication of 708 IHC prognostic biomarkers in PDAC, none has been validated for clinical use. Further research should focus on reproducibility of prognostic biomarkers in PDAC in order to achieve this.
Highlights
Pancreatic cancer remains a challenging disease, with only small improvements in overall survival rates observed in recent years [1]
In this systematic review we sought to summarise all of the existing studies of prognostic IHC biomarkers in pancreatic ductal adenocarcinoma (PDAC), and to perform a meta-analysis in relation to immune cell infiltration and prognosis
A total of 1101 articles were identified relating to the description of tissue based prognostic biomarkers in PDAC, and these investigated over 700 individual biomarkers
Summary
Pancreatic cancer remains a challenging disease, with only small improvements in overall survival rates observed in recent years [1]. There is a pressing need to conduct a systematic review to collate and assess the quality of evidence for IHC-derived prognostic biomarkers, those assessing the immune cell infiltrate, for PDAC. Previous reviews of this topic require updating and had limitations such as not conducting meta-analyses [37,38] or only using a single database to identify articles [5]. The aim of this systematic review is to summarise the quality of published studies investigating the prognostic role of immune based prognostic biomarkers in PDAC and pool the results using meta-analyses, where possible. The secondary aim is to summarise all other IHC derived prognostic biomarkers in PDAC in order to highlight areas for validation and possible gaps in evidence
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