Dataset Information

Immunotherapeutic approaches in biliary tract carcinoma: Current status and emerging strategies.

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.

SUBMITTER: Marks EI

PROVIDER: S-EPMC4644856 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Immunotherapeutic approaches in biliary tract carcinoma: Current status and emerging strategies.

Marks Eric I EI Yee Nelson S NS

World journal of gastrointestinal oncology 20151101 11

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 pe ...[more]

PMID: 26600933

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Project description:Biliary tract cancers (BTCs), comprising intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder adenocarcinoma, continue to be challenging to manage. Conventional chemotherapy regimens for advanced disease are limited in both options and benefits, and more effective perioperative regimens are also needed. Over the last decade, immunotherapy has had a profound impact on the management of many solid tumor types, particularly in using immune checkpoint inhibition to enable a tumor-directed T cell response. Immunotherapy administered on its own has had limited utility in BTCs, in part due to a hostile immune microenvironment and the relative infrequency of biomarker-based tumor-agnostic indications for immunotherapy. However, immunotherapy in conjunction with chemotherapy, molecularly targeted therapies, and/or anti-angiogenic therapies has gained traction, supported by evidence that these agents can impart favorable immunomodulatory effects on the tumor microenvironment. The TOPAZ-1 trial led to the first BTC-specific immunotherapy approval, establishing the combination of durvalumab with gemcitabine and cisplatin as the preferred first-line treatment for advanced or metastatic disease. Recently, the KEYNOTE-966 trial showed positive results for the combination of pembrolizumab with gemcitabine and cisplatin in the same setting, adding further evidence for the addition of immune checkpoint inhibition to the standard chemotherapy backbone. Meanwhile, advances in the molecular profiling of BTCs has contributed to the recent proliferation of molecularly targeted therapeutics for the subset of BTCs harboring alterations in IDH1, FGFR2, MAP kinase signaling, HER2, and beyond, and there has been great interest in investigating combinations of these agents with immunotherapy. Emerging immunotherapy strategies beyond immune checkpoint inhibition are also being studied in BTCs, and these include immunostimulatory receptor agonists, Wnt signaling modulators, adoptive cell therapy, and cancer vaccines. A large number of trials are underway to explore promising new combinations and immune-targeted strategies, offering opportunities to expand the role of immunotherapy in BTC management in the near future.

Dataset Information

Immunotherapeutic approaches in biliary tract carcinoma: Current status and emerging strategies.

Publications

Immunotherapeutic approaches in biliary tract carcinoma: Current status and emerging strategies.

Similar Datasets

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