Neopterin as a potential prognostic and predictive biomarker in metastatic renal cell carcinoma treated with immune checkpoint inhibitors

ABSTRACT

Introduction

Immunotherapy represents a significant and essential component of renal carcinoma therapy (RCC), but the selection of an optimal regimen for an individual patient remains unclear. Despite significant improvements in therapeutic options for RCC, predictive biomarkers for immunotherapeutic agents remain elusive. Neopterin is a biomarker of cell-mediated immune response, with concentrations increased in different disorders, including cancer. High neopterin levels herald, in general, a poor prognosis.

Areas covered

This review briefly overviews the contemporary clinical data on biomarkers in metastatic RCC therapy, focusing on neopterin.

Expert Opinion

Elevated neopterin levels have been observed in tumors of different primary locations. Research indicates that neopterin may serve as a potential biomarker for assessing the inflammatory status associated with certain cancers. However, it is necessary to interpret neopterin levels in the context of a comprehensive clinical evaluation, as elevated neopterin alone is not specific to cancer and can be influenced by other factors, including comorbid conditions. Neopterin has also been identified as a prognostic biomarker. An increasing neopterin level in serum and urine is associated with advanced cancer, but the role as a potential predictor of response to immunotherapy has yet to be established. A reliable biomarker for optimal therapy selection in metastatic RCC is still putative.

KEYWORDS:

• Immunotherapy
• neopterin
• predictive biomarkers
• prognostic biomarkers
• renal cell carcinoma

Article highlights

• Immune checkpoint inhibitors or a combination of an immune checkpoint inhibitor with a tyrosine kinase inhibitor represent the current gold standard in first-line metastatic RCC treatment.

• There is still a lack of predictive biomarkers routinely tested for RCC.

• Neopterin is a compound estimating immune and inflammatory status.

• Elevated neopterin alone is not specific to cancer and can be influenced by various factors. It has to be interpreted in the context of comprehensive clinical evaluation.

• The neopterin levels in serum and urine are associated with many malignant tumors, and increased neopterin concentration in peripheral blood and urine has been associated with poor prognosis.

• Neopterin is a prognostic biomarker in patients with metastatic RCC, but its predictive role in the checkpoint inhibitor era has not been proven.

• A reliable predictor of response to immunotherapy is still missing.

• There is an unmet medical need for prospective data confirming the value of inflammatory and other biomarkers as predictive tools in patients with metastatic RCC.

• Biomarkers that could be used to monitor or predict the toxicity of immunotherapy represent another unmet medical need.

Declaration of Interest

H Studentova, K Hola, B Melichar, and M Spisarova have received travel expenses for Merck Sharp & Dohme Corp and Bristol-Myers Squibb. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This manuscript was funded by Czech Science Foundation IGA_LF_2024_004.