immunity therapy for cholangiocarcinoma

Tumor mutation burden(TMB)-High is known to potentially elicit a favorable response to immune checkpoint inhibitors. In this report, we present a case of recurrent hilar cholangiocarcinoma with TMB-High, in which we performed comprehensive treatment including immune checkpoint inhibitor pembrolizumab. The patient was a 58-year-old male diagnosed with hilar cholangiocarcinoma who underwent extended right hepatectomy, caudate lobe resection, bile duct excision, and bile duct reconstruction. Postoperatively, peritoneal seeding recurrence and liver metastasis were observed, indicating TMB-High...

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed...

Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the PD1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-CTLA-4 when combined with anti-PD1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone...

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy...

OBJECTIVES: To assess the safety and efficacy of anlotinib (a multi-targeted tyrosine kinase inhibitor) combined with toripalimab (a PD-1 monoclonal antibody) in the treatment of unresectable biliary tract cancer (BTC). METHODS: In this prospective, single-arm, single-centre exploratory clinical study, patients with locally progressed or metastatic BTC were included. Patients were treated with anlotinib (12 mg, PO, QD, for 2 weeks and then stopped for a week, 21 days for a cycle) and toripalimab (240 mg, IV, Q3W)...

Cholangiocarcinoma (CCA) is a highly aggressive hepatobiliary malignancy, second only to hepatocellular carcinoma in prevalence. Despite surgical treatment being the recommended method to achieve a cure, it is not viable for patients with advanced CCA. Gene sequencing and artificial intelligence (AI) have recently opened up new possibilities in CCA diagnosis, treatment, and prognosis assessment. Basic research has furthered our understanding of the tumor-immunity microenvironment and revealed targeted molecular mechanisms, resulting in immunotherapy and targeted therapy being increasingly employed in the clinic...

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy among primary liver cancers, with an increasing overall incidence and poor prognosis. The intertumoral and intratumoral heterogeneity of ICC makes it difficult to find efficient drug therapies. Therefore, it is essential to identify tumor suppressor genes and oncogenes that induce ICC formation and progression. Here, we performed CRISPR/Cas9-mediated genome-wide screening in a liver-specific Smad4/Pten knockout mouse model (Smad4co/co ;Ptenco/co ;Alb-Cre, abbreviated as SPC), which normally generates ICC after 6 months, and detected that mutations in Trp53, Fbxw7, Inppl1, Tgfbr2, or Cul3 markedly accelerated ICC formation...

BACKGROUND: Current standard of care for advanced biliary tract cancer (BTC) is gemcitabine, cisplatin plus anti-PD1/PD-L1, but response rates are modest. The purpose of this study was to explore the efficacy and safety of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), with and without an interventional radiology (IR) procedure in advanced BTC. METHODS: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab and durvalumab for four combined doses followed by monthly durvalumab alone with and without an IR procedure until the progression of disease or unacceptable toxicity...

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunotherapeutic approaches, as well as antibody-drug conjugates...

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease's underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC...

Biliary tract cancers are molecularly and anatomically diverse cancers which include intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, and gallbladder cancer. While recognized as distinct entities, the rarer incidence of these cancers combined with diagnostic challenges in classifying anatomic origin has resulted in clinical trials and guideline recommended strategies being generalized patients with all types of biliary tract cancer. In this review, we delve into the unique aspects, subtype-specific clinical trial outcomes, and multidisciplinary management of patients with extrahepatic cholangiocarcinoma...

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) comprise the two most common primary liver malignancies. Curative treatment options often include hepatectomy or liver transplantation; however, many patients present with advanced disease that is not amenable to surgical management. In turn, many patients are treated with systemic or targeted therapy. The tumor microenvironment (TME) is a complex network of immune cells and somatic cells, which can foster an environment for disease development and progression, as well as susceptibility and resistance to systemic therapeutic agents...

Cholangiocarcinoma is a highly aggressive cancer with a dismal prognosis and limited resectability. Chemotherapy has demonstrated tremendous benefits for patients with advanced and inoperable cancer, but drug resistance poses a significant obstacle. Despite recent progress in cancer therapy, the mechanisms driving drug resistance are multifaceted and not completely comprehended. Non-coding RNA refers to RNA molecules that are endogenous and do not code for proteins. Particularly microRNAs, long non-coding RNAs, circular RNAs, are widely acknowledged to be involved in cancer initiation, proliferation, and metastasis...

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5...

BACKGROUND: Cholangiocarcinoma (CCA) poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence, resulting in a poor dismal. Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently, however, its application in CCA remains underexplored and poorly documented. CASE SUMMARY: This case report describes a patient diagnosed with stage IV CCA, accompanied by liver and abdominal wall metastases, who underwent palliative surgery...

OBJECTIVES: Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, and an urgent clinical need for new therapies. Knowledge of the CCA epigenome is largely limited to aberrant DNA methylation. Dysregulation of enhancer activities has been identified to affect carcinogenesis and leveraged for new therapies but is uninvestigated in CCA. Our aim is to identify potential therapeutic targets in different subtypes of CCA through enhancer profiling. DESIGN: Integrative multiomics enhancer activity profiling of diverse CCA was performed...

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer composed of large-duct and small-duct types. Understanding the tumor immune microenvironment and its related vascular system is important for developing novel and efficient therapies. We focused on tertiary lymphoid structure (TLS) as a hallmark of antitumor immunity and investigated the clinicopathological significance of TLSs and the influence of vascular microenvironment on TLS formation in iCCAs. We examined 261 iCCA cases clinicopathologically and analyzed the vascular system using immunohistochemistry...

The microenvironment created by tertiary lymphoid structures (TLSs) can support and regulate immune responses, affecting the prognosis and immune treatment of patients. Nevertheless, the actual importance of TLSs for predicting the prognosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients remains unclear. Herein, using spatial transcriptomic analysis, we revealed that a gene signature of TLSs specific to cHCC-CCA was associated with high-intensity immune infiltration. Then, a novel scoring system was developed to evaluate the distribution and frequency of TLSs in intra-tumoral and extra-tumoral regions (iTLS and eTLS scores) in 146 cHCC-CCA patients...

BACKGROUND: Cholangiocarcinoma (CCA) stands as an aggressive malignancy of the biliary tract. The interplay between the tumor and immune system plays a pivotal role in disease progression and treatment outcomes. Hence, the present study aimed to extensively explore the immunogenomic landscape of CCA, with the objective of unveiling unique molecular and immunological signatures that could guide personalized therapeutic approaches. METHODS: The study collected data from The Cancer Genome Atlas databases, performed gene set variation analysis for the chemokine ligand 5 (CCL5) high/low expression group, conducted principal component analysis, gene set enrichment analysis enrichment and mutation pattern analysis, generated a heatmap, and performed cox regression analysis...

Cholangiocarcinoma (CCA) is a primary malignancy which is often diagnosed when it is advanced and inoperable due to the lack of effective biomarkers and poor sensitivity of clinical diagnosis. Molecular profiling may provide information for improved clinical management, particularly targeted therapy. The study aimed to improve the understanding of molecular characteristics and its association with prognosis in Chinese CCA. We enrolled 41 Chinese patients with CCA, including 6 intrahepatic CCA (iCCA), 14 perihilar CCA (pCCA), and 21 distal CCA (dCCA) cases, all patients underwent radical operations and tumor samples underwent next-generation sequencing (NGS) by Foundation One Dx, which analyzed 324 genes...