Characterisation of the immune-related transcriptome in resected biliary tract cancers

131

124

Tumour microenvironment is a complex, multicellular functional compartment that, particularly when assembled as an abundant desmoplastic reaction, may profoundly affect the proliferative and invasive abilities of epithelial cancer cells. Tumour microenvironment comprises not only stromal cells, mainly cancer‐associated fibroblasts, but also immune cells of both the innate and adaptive system (tumour‐associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes), and endothelial cells. This results in an intricate web of mutual communications regulated by an extensively remodelled extracellular matrix, where the tumour cells are centrally engaged. In this regard, cholangiocarcinoma, in particular the intrahepatic variant, has become the focus of mounting interest in the last years, largely because of the lack of effective therapies despite its rising incidence and high mortality rates worldwide. On the other hand, recent studies in pancreatic cancer, which similarly to cholangiocarcinoma, is highly desmoplastic, have argued against a tumour‐promoting function of the tumour microenvironment. In this review, we will discuss recent developments concerning the role of each cellular population and their multifaceted interplay with the malignant biliary epithelial counterpart. We ultimately hope to provide the working knowledge on how their manipulation may lead to a therapeutic gain in cholangiocarcinoma.

Section: Mechanisms Of Immune Surveillance and Immune Escapementioning

confidence: 99%

The tumour microenvironment and immune milieu of cholangiocarcinoma

Fabris

Perugorria

Mertens

et al. 2019

131

124

“…This is particularly remarkable for BTC since they are known to arise from a background of chronic biliary duct inflammation and are characterized by an immunosuppressive milieu with reduced activation of lymphocytes with anti-tumour activity. 34 Interestingly, we highlight that the PNI is a predictive factor of response to platinum-based combination. Indeed, patients in the low-PNI group were less likely to respond to treatment (DCR 34.3% vs 61.4%) than those in the high-PNI group.…”

Section: Discussionmentioning

confidence: 82%

“…In a considerable proportion of cancer patients, it exists a vicious cycle leading to systemic inflammation, malnutrition and immunodepression that can impair patients' prognosis. This is particularly remarkable for BTC since they are known to arise from a background of chronic biliary duct inflammation and are characterized by an immunosuppressive milieu with reduced activation of lymphocytes with anti‐tumour activity …”

Section: Discussionmentioning

confidence: 99%

The prognostic nutritional index predicts survival and response to first‐line chemotherapy in advanced biliary cancer

Salati

Filippi

Vivaldi

et al. 2019

Background An accurate risk‐stratification is key to optimize the benefit‐to‐risk ratio of palliative treatment in advanced biliary cancer. We aimed at assessing the impact of the prognostic nutritional index (PNI) on survival and treatment response in advanced biliary cancer (ABC) receiving first‐line chemotherapy. Methods Medical records of ABC treated with standard chemotherapy at the Modena Cancer Centre were retrospectively reviewed for variables deemed of potential interest, including the PNI. Univariate and multivariate analyses were performed to investigate the association between the covariates and overall survival (OS). Results 114 ABC fulfilled the inclusion criteria and made up the training cohort. A PNI cut‐off value of 36.7 was established using the receiver operating characteristic (ROC) analysis. At both the univariate and the multivariate analysis, low PNI value (<36.7) was associated with shorter OS (P = .0011), together with increased NLR (P = .0046) and ECOG >1 (P < .0001). The median OS was 5.4 vs 12.1 months in the low‐ vs high PNI‐group. Moreover, a PNI value >36.7 resulted in a higher disease control in patients treated with gemcitabine/platinum combination (61.4% vs 34.3%). These results were validated in an independent cohort of 253 ABC. Conclusions We demonstrated and externally validated a prognostic role for the PNI in ABC treated with first‐line chemotherapy. Although the PNI turned out to be predictive in the subset of patients receiving platinum/gemcitabine combination, future prospective confirmation is needed.

“…Furthermore, the analysis of 53 patients with biliary tract cancer who underwent tumour resection revealed 39 transcriptomic prognostic biomarkers, all of them related with T‐cell activation and immune response. For instance, the expression levels of cytotoxic T‐lymphocyte antigen 4 (CTL4) and forkhead box P3 (FOXP3) correlated with recurrence‐free survival, suggesting an enrichment in T regulatory cells in the tumour microenvironment . Moreover, high IL‐33 tissue expression correlated with favourable prognosis in patients with iCCA or pCCA, but data on circulating IL‐33 levels were lacking.…”

Section: Biomarkers In Tumour Tissuementioning

confidence: 99%

“…For instance, the expression levels of cytotoxic T-lymphocyte antigen 4 (CTL4) and forkhead box P3 (FOXP3) correlated with recurrence-free survival, suggesting an enrichment in T regulatory cells in the tumour microenvironment. 120 Moreover, high IL-33 tissue expression correlated with favourable prognosis in patients with iCCA or pCCA, 121 but data on circulating IL-33 levels were lacking. In parallel, individual case reports have further described Granulocyte colony-stimulating factor (G-CSF)-expressing CCAs and suggested monitoring circulating G-CSF to diagnose disease relapse after radical tumour resection.…”

Section: Ta B L E 3 (Continued)mentioning

confidence: 99%

Diagnostic and prognostic biomarkers in cholangiocarcinoma

Macı́as

Kornek

Rodrigues

et al. 2019

101

The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non‐invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any known aetiological factor highly compromises the monitoring of patients at risk for tumour development and also their early diagnosis. Combination of clinical/biochemical features, imaging techniques and analysis of non‐specific tumour biomarkers in serum are commonly used to help in the diagnosis of CCA, but tumour biopsy is usually required to confirm the diagnosis. Moreover, no prognostic biomarkers are currently used in the clinical setting, deserving more innovative research, and international validation and consensus. Important efforts have been made in the last few years to identify accurate non‐invasive biomarkers, by using innovative techniques and high‐throughput omics technologies. This review summarizes and discusses the advances in the investigation of novel diagnostic and prognostic biomarkers in CCA and envisions the future directions in this field of research.