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Scientific article
Open access
English

Anti-CD122 antibody restores specific CD8+ T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth

Published inOncoimmunology, vol. 12, no. 1, 2184991
Publication date2023
First online date2023-03-02
Abstract

Nonalcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). Although immunotherapy is used as first-line treatment for advanced HCC, the impact of NASH on anticancer immunity is only partially characterized. We assessed the tumor-specific T cell immune response in the context of NASH. In a mouse model of NASH, we observed an expansion of the CD44+CXCR6+PD-1+CD8+ T cells in the liver. After intra-hepatic injection of RIL-175-LV-OVA-GFP HCC cells, NASH mice had a higher percentage of peripheral OVA-specific CD8+ T cells than control mice, but these cells did not prevent HCC growth. In the tumor, the expression of PD-1 on OVA-specific CD44+CXCR6+CD8+ cells was higher in NASH mice suggesting lowered immune activity. Treating mice with an anti-CD122 antibody, which reduced the number of CXCR6+PD-1+ cells, we restored OVA-specific CD8 activity, and reduced HCC growth compared to untreated NASH mice. Human dataset confirmed that NASH-affected livers, NASH tissues adjacent to HCC and HCC in patients with NASH exhibited gene expression patterns supporting mouse observations. Our findings demonstrate the immune system fails to prevent HCC growth in NASH, primarily linked to a higher representation of CD44+CXCR6+PD-1+CD8+ T cells. Treatment with an anti-CD122 antibody reduces the number of these cells and prevents HCC growth.

eng
Keywords
  • Hepatocellular carcinoma
  • Immunotherapy
  • Nonalcoholic steatohepatitis
  • Humans
  • Mice
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Non-alcoholic Fatty Liver Disease / therapy
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • CD8-Positive T-Lymphocytes
  • Liver Neoplasms / genetics
  • Programmed Cell Death 1 Receptor / metabolism
Citation (ISO format)
LACOTTE, Stéphanie et al. Anti-CD122 antibody restores specific CD8<sup>+</sup> T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth. In: Oncoimmunology, 2023, vol. 12, n° 1, p. 2184991. doi: 10.1080/2162402X.2023.2184991
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Identifiers
ISSN of the journal2162-4011
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