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World J Gastrointest Oncol. Nov 15, 2015; 7(11): 338-346
Published online Nov 15, 2015. doi: 10.4251/wjgo.v7.i11.338
Immunotherapeutic approaches in biliary tract carcinoma: Current status and emerging strategies
Eric I Marks, Nelson S Yee
Eric I Marks, Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, United States
Nelson S Yee, Division of Hematology-Oncology, Program of Experimental Therapeutics, Department of Medicine, Penn State Hershey Medical Center, Penn State Hershey Cancer Institute, Hershey, PA 17033-0850, United States
Author contributions: Marks EI and Yee NS conceived and designed the study, reviewed the literature, collected and analyzed the data, and wrote the paper.
Conflict-of-interest statement: The authors declare no conflict of interest in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nelson S Yee, MD, PhD, Division of Hematology-Oncology, Program of Experimental Therapeutics, Department of Medicine, Penn State Hershey Medical Center, Penn State Hershey Cancer Institute, 500 University Drive, Hershey, PA 17033-0850, United States. nyee@hmc.psu.edu
Telephone: +1-717-5310003 Fax: +1-717-5315076
Received: June 28, 2015
Peer-review started: July 11, 2015
First decision: July 28, 2015
Revised: August 17, 2015
Accepted: September 16, 2015
Article in press: September 18, 2015
Published online: November 15, 2015
Abstract

For biliary tract carcinoma (BTC), complete surgical resection of tumor is only feasible in a minority of patients, and the treatment options for patients with unresectable or metastatic disease are limited. Advances in cancer immunology have led to identification of tumor-infiltrating immune cells as indicators of prognosis and response to treatment in BTC. This has also facilitated development of immunotherapy that focuses on enhancing the immune system against biliary tumors. This includes peptide- and dendritic cell-based vaccines that stimulate in-vivo immune responses against tumor-specific antigens. Adoptive immunotherapy, which entails the ex-vivo expansion of tumor-infiltrating immune cells for subsequent reintroduction, and cytokine-based therapies have been developed in BTC. Clinical studies indicate that this type of therapy is generally well tolerated. Combination therapy with dendritic cell-based vaccines and adoptive immunotherapy has shown particularly good potential. Emerging strategies through discovery of novel antigen targets and by reversal of tumor-associated immunosuppression are expected to improve the efficacy of immunotherapy in BTC. Collaborative efforts by integration of targeted immunotherapeutics with molecular profiling of biliary tumor will hopefully make a positive impact on advancing towards the goal of developing precision treatment of patients with this highly lethal disease.

Keywords: Adoptive immunotherapy, Cancer vaccines, Biliary tract carcinoma, Cholangiocarcinoma, Gallbladder carcinoma, Immunotherapy, Precision treatment

Core tip: Advances in cancer immunology have led to development of novel therapeutics that focuses on enhancing the immune system against biliary tract cancer. These include peptide- or dendritic cell-based vaccines, adoptive immunotherapy, and immunostimulatory cytokines. Immunotherapy is generally well tolerated with good potential for developing into treatment. The efficacy of immunotherapy may be improved by reversal of tumor-associated immunosuppression and through discovery of novel antigen targets. Integration of targeted immunotherapeutics with molecular profiling of biliary tumor is expected to make a positive impact on advancing towards the goal of developing precision treatment of patients with this highly lethal disease.