Immunotherapy of gallbladder cancer

Biliary tract cancers (BTCs) arising from the epithelial cells of the biliary tree and the gallbladder represent a rare and heterogeneous group of malignancies known for their aggressive nature, encompassing cholangiocarcinoma and gallbladder cancer. Typically, diagnosis occurs in the locally advanced or metastatic stage, with approximately ۹۰% of patients are detected at advanced stages, and affected patients are usually asymptomatic in earlier stages of disease. Chronic inflammation plays an important role in the carcinogenesis of BTC, highlighting the immune etiology of this disease. systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy (IO) including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy and combination therapies (immunotherapy, immuno-oncology, targeted therapy, surgery, cytotoxic chemotherapy and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Our understanding of the tumor microenvironment and the molecular classification has led to the identification of targetable mutations, such as isocitrate dehydrogenase ۱ and fibroblast growth factor receptor ۲. Despite the identification of these genomic alterations, until recently, little advancement had been made in the first-line setting for advanced BTC. The use of immunotherapeutic agents is currently only approved for a small subset of treatment-refractory BTCs based on microsatellite instability (MSI) status and tumor mutational burden (TMB); however, this landscape may change with the anticipated approval of immunotherapy combined with chemotherapy as a result of the TOPAZ-۱ trial, and ICIs-combined chemoimmunotherapy will be poised to become a new frontline therapy option. This review will discuss the available data and evidence for immunotherapy in BTC.

کلیدواژه ها:

biliary tract cancer ، cholangiocarcinoma ، gallbladder cancer ، immune checkpoint inhibitors