# 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.

## Key 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.