Comprehensive Analysis Of Biomarkers Predicting Response To Nivolumab + Ipilimumab Combination Therapy In Cancer Treatment

Abstract

This review explores the biomarkers associated with response and resistance to the combination therapy of Nivolumab and Ipilimumab, two pivotal immune checkpoint inhibitors in the treatment of various cancers. Nivolumab, a PD-1 antagonist, and Ipilimumab, a CTLA-4 antagonist, work synergistically to enhance T-cell activation and promote anti-tumor immunity. However, patient responses to this combination are heterogeneous, underscoring the need for reliable predictive biomarkers to optimize treatment strategies.

We examine several key biomarkers, including PD-L1 expression, tumor mutational burden (TMB), microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), and circulating tumor DNA (ctDNA). Each biomarker presents unique insights into tumor biology and immune response, yet challenges such as variability in measurement, inter-patient heterogeneity, and the dynamic nature of biomarker expression complicate their clinical application. Furthermore, understanding the mechanisms underlying resistance to combination therapy, including immunosuppressive factors within the tumor microenvironment, is critical for improving therapeutic efficacy.

This review highlights the importance of developing standardized assays and multi-omics approaches that can integrate diverse biomarker data to enhance the predictive power of response assessments. Ultimately, advancing biomarker research is essential for personalizing Nivolumab + Ipilimumab therapy, ensuring that patients receive the most effective treatment based on their individual tumor characteristics and immune profiles.