Distribution of Immune Cells in Tumor Microenvironment Correlates With Checkpoint Inhibitor Response in Nasopharyngeal Carcinoma: A Multiregional Study

PURPOSE This study investigated whether the benefit of patients with recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC) from immune checkpoint inhibitor (ICI)–containing regimens was correlated with the presence of tumor microenvironment (TME) cell subpopulations that correlate with clinical outcomes. PATIENTS AND METHODS A total of 73 patients with R/M NPC from four prospective trials in three centers using nivolumab monotherapy, nivolumab + gemcitabine, nivolumab + ipilimumab, or avelumab + axitinib were included. Lunit SCOPE IO, an artificial intelligence–powered spatial TME analyzer, analyzed tumor-infiltrating lymphocytes (TILs), macrophages (MPs), fibroblasts (FBs), and endothelial cells in the intratumoral area and adjacent stroma. RESULTS The median progression-free survival (PFS) was 7.3 months, and the median overall survival (OS) was 30.0 months for the entire cohort. Higher intratumoral immune infiltrates showed association with improved treatment response, with both intratumoral TILs (hazard ratio [HR], 0.44 [95% CI, 0.24 to 0.83]; P = .0081) and intratumoral MPs (HR, 0.5 [95% CI, 0.27 to 0.91]; P = .0209) showing associations with improved PFS in the combined cohort. In contrast, stromal immune populations did not show clear correlations (stromal TILs: HR 1.14, P = .6681; stromal MPs: HR 0.9, P = .7278). Higher stromal FB density was also associated with poor outcomes, showing a trend toward shorter PFS and a significant reduction in OS (HR, 2.44 [95% CI, 1.16 to 5.11]; P < .05). CONCLUSION The results from this multinational cohort suggest that high intratumoral infiltrations of TILs and MPs, along with low stromal FB densities, may be associated with better response to ICI-containing treatment in NPC. Further studies in larger, expanded cohorts are warranted, and prospective validation is needed.