Immunology and immunotherapy of cholangiocarcinoma

Tim F Greten; Robert Schwabe; Nabeel Bardeesy; Lichun Ma; Lipika Goyal; Robin K Kelley; Xin W Wang

doi:10.1038/s41575-022-00741-4

Immunology and immunotherapy of cholangiocarcinoma

Nat Rev Gastroenterol Hepatol. 2023 Jun;20(6):349-365. doi: 10.1038/s41575-022-00741-4. Epub 2023 Jan 25.

Authors

Tim F Greten^{1

2}, Robert Schwabe^{3

4}, Nabeel Bardeesy^{5

6}, Lichun Ma⁷, Lipika Goyal⁸, Robin K Kelley⁹, Xin W Wang^{10

11}

Affiliations

¹ Gastrointestinal Malignancies Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. tim.greten@nih.gov.
² Liver Cancer Program, Bethesda, MD, USA. tim.greten@nih.gov.
³ Institute of Human Nutrition, Columbia University, New York, NY, USA.
⁴ Department of Medicine, Columbia University, New York, NY, USA.
⁵ Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁶ Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁷ Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁸ Division of Oncology, Stanford School of Medicine, Palo Alto, CA, USA.
⁹ Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
¹⁰ Liver Cancer Program, Bethesda, MD, USA.
¹¹ Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

PMID: 36697706
DOI: 10.1038/s41575-022-00741-4

Abstract

Cholangiocarcinoma is the second most common primary liver cancer. Its incidence is low in the Western world but is rising globally. Surgery, chemotherapy and radiation therapy have been the only treatment options for decades. Progress in our molecular understanding of the disease and the identification of druggable targets, such as IDH1 mutations and FGFR2 fusions, has provided new treatment options. Immunotherapy has emerged as a potent strategy for many different types of cancer and has shown efficacy in combination with chemotherapy for cholangiocarcinoma. In this Review, we discuss findings related to key immunological aspects of cholangiocarcinoma, including the heterogeneous landscape of immune cells within the tumour microenvironment, the immunomodulatory effect of the microbiota and IDH1 mutations, and the association of immune-related signatures and patient outcomes. We introduce findings from preclinical immunotherapy studies, discuss future immune-mediated treatment options, and provide a summary of results from clinical trials testing immune-based approaches in patients with cholangiocarcinoma. This Review provides a thorough survey of our knowledge on immune signatures and immunotherapy in cholangiocarcinoma.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Bile Duct Neoplasms* / therapy
Bile Ducts, Intrahepatic / pathology
Cholangiocarcinoma* / therapy
Humans
Immunotherapy / methods
Molecular Targeted Therapy / methods
Tumor Microenvironment

Abstract

Publication types

MeSH terms

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