Targeting tumor microenvironment for cholangiocarcinoma: Opportunities for precision medicine

Carloni R., Rizzo A., Ricci A. D., Di Federico A., De Luca R., GÜVEN D. C., ...More

TRANSLATIONAL ONCOLOGY, vol.25, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25
  • Publication Date: 2022
  • Doi Number: 10.1016/j.tranon.2022.101514
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Directory of Open Access Journals
  • Keywords: Cholangiocarcinoma, Tumor microenvironment, Cancer associated fibroblasts, Tumor infiltrating lymphocytes, Immunotherapy, Tumor associated macrophages, CANCER-ASSOCIATED FIBROBLASTS, BILIARY-TRACT CANCER, HUMAN INTRAHEPATIC CHOLANGIOCARCINOMA, DENDRITIC CELLS, 2ND-LINE TREATMENT, POOR-PROGNOSIS, I EXPRESSION, IMMUNE CELLS, ACTIVATION, INHIBITION
  • Hacettepe University Affiliated: Yes


Systemic treatments (e.g., chemotherapy and targeted therapies) have limited efficacy for patients with locally advanced - unresectable - and metastatic cholangiocarcinoma (CCA), with an overall survival of less than a year. Tumor microenvironment (TME) represents the ecosystem surrounding the tumor which comprises immune cells, fibroblasts, endothelial cells, and a wide range of soluble factors. CCA TME is characterized by an abundant desmoplastic stroma, exhibits a high heterogeneity and it plays a central role in cancer onset and progression. There is growing evidence suggesting that it is possible to target TME in association with other treatment modalities, such as cytotoxic chemotherapy or targeted therapies, paving the way to possible combination strategies with a synergistic effect. Herein, we describe the components of CCA TME - such as cancer-associated fibroblasts and other cells of pivotal importance - with their most relevant interactions, focusing on the preclinical rationale for the development of effective anticancer treatments.