Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug 25:13:1247614.
doi: 10.3389/fonc.2023.1247614. eCollection 2023.

Potential predictive role of gut microbiota to immunotherapy in HCC patients: a brief review

Paola Muscolino  1 , Barbara Granata  1 , Fausto Omero  1 , Claudia De Pasquale  2 , Stefania Campana  2 , Alessia Calabrò  2 , Federica D'Anna  1 , Fabiana Drommi  2 , Gaetana Pezzino  2 , Riccardo Cavaliere  2   3 , Guido Ferlazzo  4   5 , Nicola Silvestris  1 , Desirèe Speranza  1
Affiliations
Review

Potential predictive role of gut microbiota to immunotherapy in HCC patients: a brief review

Paola Muscolino et al. Front Oncol. .

Abstract

The recent evolution of immunotherapy has revolutionised the treatment of hepatocellular carcinoma (HCC) and has led to new therapeutic standards. The advances in immunotherapy have been accompanied by the recognition of the role of the gut-liver axis in the progression of HCC but also of the clinical relevance of the gut microbiota, which influences host homeostasis but also cancer development and the response to treatment. Dysbiosis, by altering the tumour microenvironment, favours the activation of intracellular signalling pathways and promotes carcinogenesis. The gut microbiota, through their composition and immunomodulatory role, are thus strong predictors of the response to immune checkpoint inhibitor (ICI) treatment as well as an available target to improve ICI efficacy and reduce drug toxicities. In this review we examine the novel role of the gut microbiota as biomarkers in both the diagnosis of HCC and the clinical response to immunotherapy as well as its potential impact on clinical practice in the future.

Keywords: advanced; biomarkers; hepatocellular carcinoma; immunotherapy; microbiota.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immune cell responses in ICI responder vs ICI non-responder patients with HCC. In patients who are ICI responders, a favourable microbiota is associated with interleukin (IL)-12-producing dendritic cells (DC) that support activation of both Th1 immune responses and cytotoxic T lymphocyte (CTL)-mediated cytotoxicity, resulting in the effective control of tumour growth. Conversely, in patients who are ICI non-responders, a dysbiotic microbiota is associated with tolerogenic DC that drive the expansion of immunosuppressive IL-10-producing T regulatory cells, thus supporting tumour progression.
Figure 2
Figure 2
Differences in the microbiota: between responders and non-responders. PFS, progression-free survival; OS, overall survival. mPFS, median progression-free survival; mOS, median overall survival; NR, not reached.
Figure 3
Figure 3
Modulators of the intestinal microbiota.
See this image and copyright information in PMC

References

    1. Temraz S, Nassar F, Kreidieh F, Mukherji D, Shamseddine A, Nasr R. Hepatocellular carcinoma immunotherapy and the potentialInfluence of gut microbiome. Int J Mol Sci (2021) 22(15):7800. doi: 10.3390/ijms22157800 - DOI - PMC - PubMed
    1. Li L, Ye J. Characterization of gut microbiota in patients with primary hepatocellular carcinoma received immune checkpoint inhibitors: A Chinese population-based study. Med (Baltimore). (2020) 99(37):e21788. doi: 10.1097/MD.0000000000021788 - DOI - PMC - PubMed
    1. Luo W, Guo S, Zhou Y, Zhao J, Wang M, Sang L, et al. Hepatocellular carcinoma: how the gut microbiota contributes to pathogenesis, diagnosis, and therapy. Front Microbiol (2022) 13:873160. doi: 10.3389/fmicb.2022.873160 - DOI - PMC - PubMed
    1. Spanu D, Pretta A, Lai E, Persano M, Donisi C, Mariani S, et al. Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment. World J Hepatol (2022) 14(7):1319–32. doi: 10.4254/wjh.v14.i7.1319 - DOI - PMC - PubMed
    1. Shen S, Khatiwada S, Behary J, Kim R, Zekry A. Modulation of the gut microbiome to improve clinical outcomes in hepatocellular carcinoma. Cancers (Basel). (2022) 14(9):2099. doi: 10.3390/cancers14092099 - DOI - PMC - PubMed

LinkOut - more resources