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CDK20 inhibition and immune checkpoint blockade: bringing cancer biology and tumour immunology together to develop novel treatment options for HCC
  1. Tim F Greten,
  2. Firouzeh Korangy
  1. Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Professor Tim F Greten, Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch,Center for Cancer Research, National Cancer Institute, National Institutes of Health, NCI, 9000 Rockville Pike Bethesda MD 20892, USA; tim.greten{at}nih.gov

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On 22 September 2017 the Food and Drug Administration granted accelerated approval to nivolumab for the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib. Approval was based on a 154-patient subgroup of a multicentre, open-label trial conducted in patients with HCC and Child-Pugh A cirrhosis who progressed on or were intolerant to sorafenib.1 With an overall response rate of close to 15%, which lasted in more than 90% of the patients 6 months or longer, immune checkpoint blockade has become a treatment option for patients with HCC after many years of failures in drug development. However, these data also call for future combination studies, which will increase the number of patients responding to immunotherapy. But what is the best combination partner for an immune checkpoint inhibitor in HCC?

While immune checkpoint inhibitors successfully lead to activation of T cells in patients with HCC,2 they have no effect on the microenvironment and possible immunosuppressive mechanisms such as regulatory T cells and myeloid-derived suppressor cells (MDSCs). MDSCs represent a population of immature myeloid cells, composite of two major subsets, monocytic CD14+ …

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