Predictive Biomarkers in Immunotherapy for Advanced Melanoma

Advanced melanoma remains a formidable clinical challenge, driven by its high mutational burden and capacity for immune evasion. The introduction of immune checkpoint inhibitors—principally antibodies against PD-1 and CTLA-4—has revolutionised therapy, yet only a subset of patients derive long-term benefit. Predictive biomarkers aim to forecast response, guide patient selection and manage toxicity. Tissue-based markers, including PD-L1 expression and tumour mutational burden, inform on the likelihood of effective immune-mediated tumour eradication, while blood-based markers such as lactate dehydrogenase, neutrophil-to-lymphocyte ratio and circulating tumour DNA offer minimally invasive insights into systemic immunity and tumour dynamics. Advances in plasma proteomics, transcriptomic signatures and gut microbiome profiling further expand the biomarker repertoire. Harnessing these indicators through computational models holds global significance for optimising immunotherapy regimens, reducing adverse events and delivering personalised care across diverse healthcare settings.

Research from Nature Portfolio

Recent studies have employed longitudinal plasma proteome profiling in patients receiving combined PD-1 and CTLA-4 blockade, unveiling dynamic alterations in cholesterol metabolism and identifying APOC3 among a panel of proteins predictive of dual-blocker therapy response. Machine learning algorithms integrating proteomic and radiological data achieved high accuracy in forecasting clinical outcomes. Another investigation adopted a systems biology approach to analyse paired blood and tumour samples, revealing that PD-L1 expression on peripheral T cells and CD137-positive CD8+ lymphocytes correlate with progression-free and overall survival following checkpoint inhibition. These findings underscore the value of circulating immune markers and high-dimensional profiling for real-time prediction of immunotherapy benefit.

Predictive Biomarkers in Immunotherapy for Advanced Melanoma publication trend

The graph below shows the total number of articles in predictive biomarkers in immunotherapy for advanced melanoma across all publications each year (not limited to Nature Index journals).

Technical terms

Programmed cell death protein 1 (PD-1): an immune checkpoint receptor on T cells that downregulates immune responses upon binding its ligand PD-L1.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4): an inhibitory receptor on T cells that modulates early stages of T cell activation.

Tumour mutational burden (TMB): the total number of somatic mutations per coding area of a tumour genome, reflecting neoantigen load.

Circulating tumour DNA (ctDNA): fragments of tumour-derived DNA detectable in peripheral blood, used to monitor tumour dynamics.

Neutrophil-to-lymphocyte ratio (NLR): the ratio of absolute neutrophil to lymphocyte counts, serving as a marker of systemic inflammation.

Proteome profiling: the large-scale analysis of proteins in biological samples to identify patterns associated with disease states or treatment response.

References

1. Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy. Nature Communications (2024).
2. CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy. Journal of Translational Medicine (2023).
3. Prognostic value of inflammatory markers NLR, PLR, LMR, dNLR, ANC in melanoma patients treated with immune checkpoint inhibitors: a meta-analysis and systematic review. Frontiers in Immunology (2024).
4. Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers. British Journal of Cancer (2017).