Qualification of tumour mutational burden by targeted next‐generation sequencing as a biomarker in hepatocellular carcinoma

Wong, Ching Ngar; Fessas, Petros; Dominy, Kathy; Mauri, Francesco; Kaneko, Takahiro; Parcq, Persephone Du; Khorashad, Jamshid S.; Toniutto, Pierluigi; Goldin, Robert; Avellini, Claudio

doi:10.1111/liv.14706

Cited by 39 publications

(25 citation statements)

References 33 publications

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“…Furthermore, PD-L1 positivity was not associated with high TMB, where several patients with high positive PD-L1 were also TMB low (2-5 mutations/Mb)[ 122 ]. These data were confirmed by more recent studies showing that TMB could not predict OS and patient’s responsiveness to anti-PD-1[ 123 - 125 ]. Besides, HCC had low levels of microsatellite instability, a phenotype due to accumulated mutations resulting from a defect in mismatch repair[ 126 ].…”

Section: Biomarkers For Anti-pd-1/pd-l1 Icissupporting

confidence: 68%

Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Sukowati

El-Khobar

Tiribelli

2021

WJSC

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Hepatocellular carcinoma (HCC) is a heterogeneous malignancy related to diverse etiological factors. Different oncogenic mechanisms and genetic variations lead to multiple HCC molecular classifications. Recently, an immune-based strategy using immune checkpoint inhibitors (ICIs) was presented in HCC therapy, especially with ICIs against the programmed death-1 (PD-1) and its ligand PD-L1. However, despite the success of anti-PD-1/PD-L1 in other cancers, a substantial proportion of HCC patients fail to respond. In this review, we gather current information on biomarkers of anti-PD-1/PD-L1 treatment and the contribution of HCC heterogeneity and hepatic cancer stem cells (CSCs). Genetic variations of PD-1 and PD-L1 are associated with chronic liver disease and progression to cancer. PD-L1 expression in tumoral tissues is differentially expressed in CSCs, particularly in those with a close association with the tumor microenvironment. This information will be beneficial for the selection of patients and the management of the ICIs against PD-1/PD-L1.

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Section: Biomarkers For Anti-pd-1/pd-l1 Icissupporting

confidence: 68%

Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Sukowati

El-Khobar

Tiribelli

2021

WJSC

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“…Tissue-agnostic biomarkers such as tumour mutation burden (TMB) and MSI have been examined for cancer immunotherapy [57][58][59]. TMB has been utilised as a predictive biomarker in cancer immunotherapy in several studies [11,[60][61][62]. Our previous study demonstrated significant association of TMB with poor clinical outcomes in HCC patients [11].…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint molecules are regulated by transforming growth factor (TGF)-β1-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma

et al. 2021

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“…Recently, Wong et al evaluated the TMB in 29 HCC patients through targeted next-generation sequencing (tNGS) on both fresh and archival samples. The authors reported that, while fresh HCC samples were better sources of tumor DNA (45), the low median TMB values observed may limit the usefulness of the TMB as a predictor of response to immunotherapy in HCC.…”

Section: Tumor Mutational Burden/microsatellite Instabilitymentioning

confidence: 99%

Biomarkers and Future Perspectives for Hepatocellular Carcinoma Immunotherapy

Che

et al. 2021

Front. Oncol.

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Hepatocellular cancer is the sixth most frequently diagnosed malignant disease worldwide, and was responsible for tens of millions of deaths in 2020; however, treatment options for patients with advanced hepatocellular carcinoma remain limited. Immunotherapy has undergone rapid development over recent years, especially in the field of immune checkpoint inhibitors (ICIs). These drugs aim to activate and enhance antitumor immunity and represent a new prospect for the treatment of patients with advanced cancer. Nevertheless, only a small proportion of liver cancer patients currently benefit from ICI-based treatment, highlighting the need to better understand how ICIs and tumors interact, as well as identify predictive biomarkers for immunotherapeutic responses. In this review, we highlight clinical trials and basic research in hepatocellular carcinoma, with a particular focus on predictive biomarkers for the therapeutic efficacy of ICIs. Predictive biomarkers for immune-related adverse events are also discussed.

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Qualification of tumour mutational burden by targeted next‐generation sequencing as a biomarker in hepatocellular carcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 39 publications

References 33 publications

Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Immune checkpoint molecules are regulated by transforming growth factor (TGF)-β1-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma

Biomarkers and Future Perspectives for Hepatocellular Carcinoma Immunotherapy

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