Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)

Abstract

Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy originating from the epithelial system of the bile ducts, and its incidence in recent years is steadily increasing. The immune microenvironment of CCA is characterized by diversity and complexity, with a substantial presence of cancer-associated fibroblasts and immune cell infiltration, which plays a key role in regulating the distinctive biological behavior of cholangiocarcinoma, including tumor growth, angiogenesis, lymphangiogenesis, invasion and metastasis. Despite the notable success of immunotherapy in the treatment of solid tumors in recent years, patients with CCA have responded poorly to immune checkpoint inhibitor therapy. The interaction of tumor cells with cellular components of the immune microenvironment can regulate the activity and function of immune cells and form an immunosuppressive microenvironment, which may cause ineffective immunotherapy. Therefore, the components of the tumor immune microenvironment appear to be novel targets for immune therapies. Combination therapy focusing on immune checkpoint inhibitors is a promising and valuable first-line or translational treatment approach for intractable biliary tract malignancies. The present review discusses the compositional characteristics and regulatory factors of the CCA immune microenvironment and the possible immune escape mechanisms. In addition, a summary of the advances in immunotherapy for CCA is also provided. It is hoped that the present review may function as a valuable reference for the development of novel immunotherapeutic strategies for CCA.

SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment

“…Cholangiocarcinoma (CCA) is the second most common primary liver cancer globally; approximately 10% of all CCA are intrahepatic, while 90% are extrahepatic [1,2]. Although defined risk factors are known, for reasons unclear, the incidence of CCA is increasing [1,3]. An estimated 2000-8000 Americans are diagnosed with CCA each year, and the relative resistance of this tumor to chemotherapy is a major reason for an overall dismal prognosis [4].…”

Causal relationship between immune cell phenotypes and risk of biliary tract cancer: evidence from Mendelian randomization analysis

“…In the tumor microenvironment of cholangiocarcinoma, tumor-associated Immune cells, including macrophages, B cell, and T cell interact with the tumor microenvironment to inhibit tumor formation. Immune cells significantly influence the regulation of distinct biological processes in CCA, encompassing invasion, angiogenesis, lymphangiogenesis, tumor growth, and metastasis, which are also associated with the clinical prognosis of this cancer ( 17 ). These investigations into the role of immune cells in biliary tract cancer offer novel insights into potential immunotherapeutic approaches for the condition.…”