Abstract
Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan–Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. Transcript ProfilingNanostring data have been submitted to GEO repository: GSE90698 and GSE90699.
Highlights
Biliary tract cancers (BTCs) arise from the epithelium of bile ducts and gallbladder [1]
To investigate if the transcriptomic immune profile is deregulated in BTC, we started by performing a comprehensive immune profiling of 770 immune-related transcripts in tumour tissue (TT) and adjacent tissue (AT) of a set including 22 resected BTCs
Loss of immune response in BTCs is associated with lack of peritumoural inflammatory infiltrate and poorer survival [27,28]
Summary
Biliary tract cancers (BTCs) arise from the epithelium of bile ducts and gallbladder [1]. Intrahepatic (ICC) and extrahepatic (ECC) CCAs harbour at least partially different molecular features, the clinical management of BTC does not differ according to the subtypes [2e4]. In phase III clinical trials, ICC, ECC and gallbladder cancers are grouped together as BTCs [5,6]. The BILCAP study suggests that adjuvant chemotherapy can improve the outcome of resected BTCs [9]. It is likely that the discovery of prognostic factors associated with the biological aggressiveness of these tumours will guide the post-surgical management of BTCs. Recent evidence suggests that the host immune response modulates the effect of chemotherapy in solid tumours [10,11]. We aimed at characterising the deregulation of immune-related transcripts in resected BTCs and exploring their potential as prognostic markers
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