Abstract
Intrahepatic, perihepatic, and hilar bile duct cancers are defined as cholangiocarcinoma (CCA). Cholangiocarcinomas constitute approximately 3% of all gastrointestinal system malignancies. The main treatment in the nonmetastatic stage is surgery. In metastatic or unresectable disease, the main treatment is systemic therapy, and there is no effective treatment response. Five-year survival in these patients is around 4.1%. With gemcitabine plus cisplatin, which is the standard first-line treatment in metastatic biliary tract cancer (BTC), the median overall survival (mOS) is 11.7 months. Again, with FOLFOX chemotherapy, which is the standard treatment in the second line, the mOS is 5.6 months. Therefore, the search for treatments with more effective response rates and survival results in BTCs continues rapidly. In recent years, with the publication of the cancer genome atlas, the tumor microenvironment has become more understandable. Along with these developments, it has been reported that the most important molecular mechanisms involved in the pathogenesis of CCA are Wnt/β-catenin and nuclear factor kappa B signaling pathways, and these mechanisms play a role in the formation and progression of CCA. The tumor microenvironment is a complex environment that influences the proliferative and invasive properties of epithelial cancer cells. Cancer cells, normal cells, mesenchymal stem cells, fibroblasts, pericytes, adipocytes, follicular dendritic cells, cancer-associated fibroblasts, mesenchymal stem cells, tumor-associated macrophages, regulatory T cells, dendritic cells, cytokines, growth factors, and extracellular matrix constituent components. After this information, immunotherapy with immune checkpoint inhibitors has been proven to be effective in solid cancers such as malign melanoma, metastatic renal cell cancer, and non-small cell lung cancer, and the investigation of the effectiveness of these treatments in other cancer types has accelerated. First, second-subsequent line monotherapy immunotherapy studies were conducted and all are phases 1 and 2, with objective response rates (ORR) reported between 5% and 35%. Afterward, especially in the first line, combination immunotherapy studies, mostly phase 2, were conducted, and the ORR was reported to be around 75% in these studies. These results suggest that first-line immunotherapy combination practices will become the standard of care in the near future.
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Korkmaz, M., Artaç, M. (2022). Tumor Microenvironment and Immunotherapy in Advanced Biliary Tract Cancers. In: Rezaei, N. (eds) Hepatobiliary Cancers: An Interdisciplinary Approach. Interdisciplinary Cancer Research, vol 3. Springer, Cham. https://doi.org/10.1007/16833_2022_41
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