Cholangiocarcinoma AND (immunotherapy OR CAR-T OR TILs)

For decades, treatment of advanced biliary tract cancer (BTC) was confined to the use of chemotherapy. In recent years however, the number of therapeutic options available for patients with unresectable BTC have drastically increased, with immunotherapy and targeted treatment gradually joining the ranks of guideline-recommended treatment regimens. The aim of the present review is to summarise the current knowledge on unresectable BTC focusing on epidemiology, anatomical distribution and current strategies for systemic treatment...

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues...

BACKGROUND: Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy...

Immune checkpoint inhibitors (ICIs) are a group of drugs that have improved outcomes for patients with various cancers. Generally considered safe and well tolerated, these drugs are occasionally linked to immune-mediated or immune-related adverse events. Among these, autoimmune neurological events are rare, displaying varying incidence rates across different studies. Peripheral neuropathy, although one of the more common neurological immune-related events, is at times underestimated. This case report highlights an adult patient diagnosed with metastatic intrahepatic cholangiocarcinoma...

Background: Previous studies have shown that cellular senescence is strongly associated with tumorigenesis and the tumor microenvironment. Accordingly, we developed a novel prognostic signature for intrahepatic cholangiocarcinoma (ICCA) based on senescence-associated long non-coding RNAs (SR-lncRNAs) and identified a lncRNA-miRNA-mRNA axis involving in ICCA. Methods: Based on the 197 senescence-associated genes (SRGs) from Genacards and their expression in Fu-ICCA cohort, we identified 20 lncRNAs as senescence-associated lncRNAs (SR-lncRNAs) through co-expression and cox-regression analysis...

This editorial contains comments on the article "Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature" in the recent issue of World Journal of Gastrointestinal Surgery . It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation (ELRAT) and systemic therapy, underlying molecular mechanisms for targeted therapy in perihilar cholangiocarcinoma (pCCA) management...

Due to the fact biliary tract cancer (BTC) is often diagnosed at an advanced stage, thus, not eligible for resection, and due to the aggressive tumor biology, it is considered as one of the cancer types with the worst prognosis. Advances in diagnosis, surgical techniques, and molecular characterization have led to an improvement of the prognosis of BTC patients, recently. Although neoadjuvant therapy is expected to improve surgical outcomes by reducing tumor size, its routine is not well established. The application of neoadjuvant therapy in locally advanced disease may be indicated, the routine use of systemic therapy prior to surgery for cholangiocarcinoma patients with an upfront resectable disease is less well established, but discussed and performed in selected cases...

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with high lethality. Clonorchis sinensis (C. sinensis) infection is an important risk factor for ICC. Here we investigated the clinical impact and underlying molecular characteristics of C. sinensis-infected ICC. METHODS: We performed single-cell RNA sequencing, whole exome sequencing, RNA-sequencing, metabolomics and spatial transcriptomics in 251 ICC patients from three medical centers...

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma...

INTRODUCTION: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC...

Advanced intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by limited response to standard therapeutic modalities, such as radiotherapy, chemotherapy, and targeted therapy. The prognosis for patients with advanced ICC is exceedingly bleak, with an overall survival of less than 1 year. In recent years, personalized neoantigen vaccines have emerged as a promising approach to augment the immune response against tumors. Clinical investigations are currently underway to evaluate the efficacy of neoantigen-based peptide, DNA, and dendritic cell vaccines...

BACKGROUND: Cholangiocarcinoma (CCA) is a rare and aggressive gastrointestinal cancer. Unfortunately, 60% to 70% of early-stage CCA patients experience disease recurrence after curative resection and standard adjuvant therapy. Currently, there is no reliable tool to identify CCA recurrence before radiographic detection. Longitudinal monitoring of circulating tumor DNA (ctDNA) has shown promising value in molecular identification of relapse prior to conventional surveillance in other solid tumors...

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a poorly immunogenic malignancy with limited survival. Syngeneic, immunocompetent mouse models of CCA are an essential tool to elucidate the tumor immune microenvironment (TIME), understand mechanisms of tumor immune evasion, and test novel immunotherapeutic strategies. The scope of this study was to develop and characterize immunocompetent CCA models with distinct genetic drivers, and correlate tumor genomics, immunobiology, and therapeutic response...

Biliary tract cancers (BTCs), consisting of intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, are an aggressive, heterogeneous malignancy. They are most often diagnosed in the locally advanced or metastatic setting, at which point treatment consists of systemic therapy or best supportive care. Our understanding of the tumor microenvironment and the molecular classification has led to the identification of targetable mutations, such as isocitrate dehydrogenase 1 and fibroblast growth factor receptor 2...

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the first and second most common primary liver cancer (PLC). For decades, systemic therapies consisting of tyrosine kinase inhibitors (TKIs) or chemotherapy have formed the cornerstone of treating advanced-stage HCC and CCA, respectively. More recently, immunotherapy using immune checkpoint inhibition (ICI) has shown anti-tumour reactivity in some patients. The combination regimen of anti-PD-L1 and anti-VEGF antibodies has been approved as new first-line treatment of advanced-stage HCC...

Biliary tract cancers continue to increase in incidence and have a high mortality rate. Most of the patients present with advanced-stage disease. The discovery of targetable genomic alterations addressing IDH, FGFR, HER2, BRAFV600 E, and others has led to the identification and validation of novel therapies in biliary cancer. Recent advances demonstrating an improved outcome with the addition of immune checkpoint inhibitors to chemotherapy have established a new first-line care standard. In case of contraindications to the use of checkpoint inhibitors and the absence of targetable alterations, chemotherapy remains to be the standard of care...

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies...

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e...

The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment...

BACKGROUND: Cholangiocarcinoma is a kind of epithelial cell malignancy with high mortality. Intratumor heterogeneity (ITH) is involved in tumor progression, aggressiveness, treatment resistance, and disease recurrence. METHODS: Integrative machine learning procedure including 10 methods (random survival forest, elastic network, Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox, supervised principal components, generalized boosted regression modeling, and survival support vector machine) was performed to construct an ITH-related signature (IRS) for cholangiocarcinoma...