Which role for predictors of response to immune checkpoint inhibitors in hepatocellular carcinoma?

ABSTRACT

Introduction

Hepatocellular carcinoma (HCC) remains a frequently diagnosed malignancy worldwide, still representing an important cause of cancer-related death. Recent years have seen the emergence of novel systemic treatments for HCC patients, including immune checkpoint inhibitors (ICIs). Nonetheless, several questions regarding HCC immunotherapy remain unanswered, especially in terms of biochemical predictors of response.

Areas Covered

In the current paper, we will discuss available evidence regarding predictive biomarkers of response to HCC immunotherapy. A literature search was conducted in January 2022 of Pubmed/Medline, Cochrane library, and Scopus databases.

Expert Opinion

The identification of predictive biomarkers represents an unmet need in HCC patients receiving ICIs. The HCC medical community is called to further efforts aimed to elucidate the effective role of PD-L1 expression, TMB, MSI, gut microbiota, and other emerging biomarkers.

KEYWORDS:

• HCC
• hepatocellular carcinoma
• PD-L1
• TMB
• immunotherapy
• human microbiota

Article highlights

• Identifying reliable predictors of response to HCC immunotherapy is needed to better modulate the therapeutic process

• Approximately 70% of advanced HCC patients treated with ICIs do not benefit from immunotherapy.

• Further translational ‘efforts’ are mandatory in this setting to optimize the use of immunotherapy in HCC, and combinations of several biomarkers have the potential to be more impactful compared to a unique predictor of response, which has already shown important limitations in this setting.

• Not only PD-L1, MTB, MSI, but also novel focuses of research are under development, including gut microbiome.

• The identification of predictive biomarkers of response to ICIs remains of pivotal importance, especially considering that the number of indications and patients receiving ICIs is supposed to further increase soon.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.