Prospective trial of immunologic signatures of response to immune checkpoint inhibition in metastatic cancer

Identifying pan-cancer tumor biomarkers that predict responses to immune checkpoint inhibitors (ICIs) is critically needed. In the multicenter AMADEUS clinical trial, patients with various advanced solid tumors were grouped based on tumoral CD8 levels: those with CD8 < 15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4), and those with CD8 ≥ 15% received nivolumab monotherapy. Seventy-nine patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (95% CI 15.8-35.2) in CD8-low and 14.3% (1.1-43.8) in CD8-high. Tumors from 35.9% (95% CI 21.8-51.4) of patients converted from CD8 < 15% pretreatment to ≥ 15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.