4.7 Review

The immunological and metabolic landscape in primary and metastatic liver cancer

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NATURE REVIEWS CANCER
卷 21, 期 9, 页码 541-557

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NATURE PORTFOLIO
DOI: 10.1038/s41568-021-00383-9

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  1. European Research Council (ERC) Consolidator grant (HepatoMetaboPath) [SFBTR179, 272983813, SFB/TR 209, 314905040, SFBTR1335, 360372040, SFB 1479, 441891347]
  2. Wilhelm Sander-Stiftung
  3. Research Foundation Flanders (FWO) [30826052]
  4. Deutsche Krebshilfe projects [70113166, 70113167]
  5. German-Israeli Cooperation in Cancer Research (DKFZ-MOST)
  6. Helmholtz-Gemeinschaft, Zukunftsthema 'Immunology and Inflammation' [ZT-0027]

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This review discusses the unique immunological and metabolic features of the liver during cancer development, and how these factors can impact the development of primary liver cancer and liver metastases. The liver is often influenced by chronic inflammation and metabolic alterations, which may affect cancer metastasis.
This Review discusses the unique and complex immunological and metabolic features of the liver, from the precancerous stage through to oncological transformation and metastasis. Strategies for targeting this niche are also considered. The liver is the sixth most common site of primary cancer in humans, and generally arises in a background of cirrhosis and inflammation. Moreover, the liver is frequently colonized by metastases from cancers of other organs (particularly the colon) because of its anatomical location and organization, as well as its unique metabolic and immunosuppressive environment. In this Review, we discuss how the hepatic microenvironment adapts to pathologies characterized by chronic inflammation and metabolic alterations. We illustrate how these immunological or metabolic changes alter immunosurveillance and thus hinder or promote the development of primary liver cancer. In addition, we describe how inflammatory and metabolic niches affect the spreading of cancer metastases into or within the liver. Finally, we review the current therapeutic options in this context and the resulting challenges that must be surmounted.

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