Throughout the last decade, we’ve witnessed significant progress in survival outcomes for advanced melanoma patients thanks to FDA approval of immune checkpoint inhibitors (ICIs), as well as BRAF and MEK targeted inhibitors. It is believed that resistance to ICIs may be caused by exclusion of T cells in the tumor microenvironment (TME), high levels of immunosuppressive cells or factors, and/or tumor mutations that result in immune ignorance, such as disruption of antigen processing and presentation. This suggests the necessity for applying broad peripheral immune and tumor profiling before and during treatment.
In a recently published study in JITC, researchers investigated the efficacy and safety of the ICI ipilimumab alone and in combination with nivolumab in advanced melanoma patients with progressive disease after PD-1 blockade as monotherapy.
IsoPlexis’ Functional Phenotyping Uncovers Key Drivers of Increased IFN-g and Decreased IL-10 in Melanoma Patients
Researchers conducted a randomized multicenter Phase II trial in patients with advanced melanoma. Participants received 1 mg/kg of nivolumab plus 3 mg/kg of ipilimumab or 3 mg/kg of ipilimumab every three weeks for up to four doses.
Patients were ranked by histological subtype as well as response to previous PD-1 therapy. The main clinical objective was overall response rate by week 18. Translational biomarker analyses were conducted in patients with blood and tissue samples.1
IsoPlexis’ single-cell functional proteomics platform identified the clinical benefit of increased effector cytokine polyfunctionality, decreased regulatory cytokine polyfunctionality, and decreased IL-10 secretion frequency from superhero CD4+ T cells, demonstrating higher patient response to the combined immunotherapies.
Single-Cell Functional Biomarkers Predict Patient Response to ICIs
Objective responses were seen in PD-1-resistant patients treated with ipilimumab alone and ipilimumab plus nivolumab, with similar disease control rates (DCRs) at week 18. Overall, the data suggest that ipilimumab-based therapies broadly engage the innate and adaptive arms of the immune response, resulting in clinical benefit.1
With the use of IsoPlexis’ functional phenotyping, key drivers of increased IFN-g and decreased IL-10 were uncovered. This is yet another example that demonstrates the power of single-cell peripheral functional biomarkers in predicting patient response to checkpoint inhibitor immunotherapy.
This study underscores the significance of IsoPlexis’ unique metric PSI (Polyfunctional Strength Index) in assessing therapeutic efficacy in Phase II clinical trials.
- Friedman CF, Spencer C, Cabanski CR, et al. Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses. Journal for ImmunoTherapy of Cancer 2022;10:e003853. doi: 10.1136/jitc-2021-003853