Abstract
Simple SummaryIn this review, we discuss treatment strategies in biliary tract cancers (gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma). In particular, we will describe advances in cellular therapies and cancer vaccines for biliary tract cancers, followed by our local experience with combining a melanoma-associated antigen (MAGE)-positive cell lysate-based autologous dendritic cell vaccine and anti-angiogenic therapy (bevacizumab) in a case of stage IV gallbladder cancer.Biliary tract cancer (BTC) is a rare, but aggressive, disease that comprises of gallbladder carcinoma, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with heterogeneous molecular profiles. Advanced disease has limited therapeutic options beyond first-line platinum-based chemotherapy. Immunotherapy has emerged as a viable option for many cancers with a similar unmet need. Therefore, we reviewed current understanding of the tumor immune microenvironment and recent advances in cellular immunotherapy and therapeutic cancer vaccines against BTC. We illustrated the efficacy of dendritic cell vaccination in one patient with advanced, chemorefractory, melanoma-associated antigen (MAGE)-positive gallbladder carcinoma, who was given multiple injections of an allogenic MAGE antigen-positive melanoma cell lysate (MCL)-based autologous dendritic cell vaccine combined with sequential anti-angiogenic therapy. This resulted in good radiological and tumor marker response and an overall survival of 3 years from diagnosis. We postulate the potential synergism of adding anti-angiogenic therapy, such as bevacizumab, to immunotherapy in BTC, as a rational scientific principle to positively modulate the tumor microenvironment to augment antitumor immunity.
Highlights
Biliary tract cancer (BTC) is a rare but clinically aggressive cancer that accounts for 3–5% of cancer diagnoses globally
FGF2 all higher plasma cytokine levels of IL-1a, IL-1b, IL-2, IL-6, IL-10, vascular endothelial growth factor (VEGF) and FGF2 were all higher than baseline reference ranges for healthy individuals, they were found to decrease during periods of treatment than baseline reference ranges for healthy individuals, they were found to decrease during periods of treatment response compared to pre-treatment and disease progression time points (Figure 3)
Encouraging clinical signals are seen in earlier clinical trials of therapeutic cancer vaccination and adoptive T-cell therapy in these patients, indicating a potential, emerging role for cellular immunotherapy against BTC
Summary
Biliary tract cancer (BTC) is a rare but clinically aggressive cancer that accounts for 3–5% of cancer diagnoses globally. It is a heterogeneous disease comprising gallbladder carcinoma (GBC), Cancers 2020, 12, 3404; doi:10.3390/cancers12113404 www.mdpi.com/journal/cancers. Cancers 2020, 12, 3404 intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC). With an increased understanding of the differing anatomical, histological and molecular subtypes of biliary tract cancers, novel therapies have emerged in the last two decades. Chemotherapy remains the standard of care in first-line metastatic biliary tract cancers with modest efficacy. More research efforts are required in the subsequent lines of treatment for patients with advanced stage disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
