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Neutrophils as potential therapeutic targets in hepatocellular carcinoma

Lookup NU author(s): Dr Daniel Geh, Dr Jack LeslieORCiD, Professor Helen ReevesORCiD, Professor Derek Mann


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© 2022, Springer Nature Limited.The success of atezolizumab plus bevacizumab treatment contributed to a shift in systemic therapies for hepatocellular carcinoma (HCC) towards combinations that include cancer immunotherapeutic agents. Thus far, the principal focus of cancer immunotherapy has been on interrupting immune checkpoints that suppress antitumour lymphocytes. As well as lymphocytes, the HCC environment includes numerous other immune cell types, among which neutrophils are emerging as an important contributor to the pathogenesis of HCC. A growing body of evidence supports neutrophils as key mediators of the immunosuppressive environment in which some cancers develop, as well as drivers of tumour progression. If neutrophils have a similar role in HCC, approaches that target or manipulate neutrophils might have therapeutic benefits, potentially including sensitization of tumours to conventional immunotherapy. Several neutrophil-directed therapies for patients with HCC (and other cancers) are now entering clinical trials. This Review outlines the evidence in support of neutrophils as drivers of HCC and details their mechanistic roles in development, progression and metastasis, highlighting the reasons that neutrophils are well worth investigating despite the challenges associated with studying them. Neutrophil-modulating anticancer therapies entering clinical trials are also summarized.

Publication metadata

Author(s): Geh D, Leslie J, Rumney R, Reeves HL, Bird TG, Mann DA

Publication type: Review

Publication status: Published

Journal: Nature Reviews Gastroenterology and Hepatology

Year: 2022

Online publication date: 12/01/2022

Acceptance date: 06/12/2021

ISSN (print): 1759-5045

ISSN (electronic): 1759-5053

Publisher: Nature Research


DOI: 10.1038/s41575-021-00568-5