Ipilimumab, -omics, and head and neck cancers—update in 2025

TL;DR

This paper reviews the use of ipilimumab and nivolumab in treating head and neck cancers, highlighting their efficacy, side effects, and the role of the gut microbiome in treatment outcomes.

Contribution

The paper provides an updated analysis of ipilimumab-based immunotherapy in head and neck cancers, emphasizing the microbiome's role in treatment response and toxicity.

Findings

Combining ipilimumab with nivolumab increases gastrointestinal side effects in head and neck cancer patients.

The gut microbiome influences both the efficacy and adverse events of ipilimumab-based immunotherapy.

Data on microbiome effects in head and neck cancers remain limited despite their importance in immunotherapy outcomes.

Abstract

Immunotherapy employing immune checkpoint inhibitors (ICIs) represents a pivotal approach for the management of recurrent and metastatic head and neck cancers (HNCs). Ipilimumab is a fully human monoclonal IgG1κ antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4), which can be introduced as a monotherapy or dual immunological regimen with nivolumab (anti-programmed death protein 1, PD-1). The background of the use of these monoclonal antibodies as combination immunotherapy is strongly associated with their different mechanisms of action. CTLA-4 and PD-1 are able to regulate the function of T cells through different mechanisms. Despite the better efficacy of immunotherapy with ipilimumab + nivolumab in HNCs observed in some cases, the overall effect regarding the comparison of ipilimumab versus ipilimumab + nivolumab is still unclear. The microbiome is one of the biomarkers that affect the response to immunotherapy with ICIs, including ipilimumab. Nevertheless, there is a clear lack of data in this context with regard to HNCs. The beneficial signature of the microbiome contributes to the prevention of the immune-related adverse events caused by ipilimumab. Notably, the incidence of gastrointestinal side effects induced by ICIs is significantly increased in the dual regimen with ipilimumab + nivolumab, which affects its recommendation for patients with HNCs

Diagram illustrating the relationship between immune checkpoint inhibitor-based immunotherapy, gut microbiome, and outcomes in head and neck cancers. Treatments include nivolumab, ipilimumab, or both, impacting efficacy and immune-related adverse events, while gut microbiome composition can modify these effects.

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