Clinical validation of iRIS in independent non–small cell lung cancer cohort. An independent cohort of 59 non–small cell lung cancer (NSCLC) patients treated with postoperative radiation at various doses (range: 42–70 Gy) were analyzed for locoregional control (LRC), failure (LRF) or overall survival (OS). (A) iRIS is not correlated with the total radiation dose delivered to the 59 NSCLC patients (r = -0.24, P < 0.06). Color code: patient samples with locoregional control (LRC, green) and locoregional failure (LRF, red). (B) left panel, The inferred cellular composition (immune cell infiltrates and malignant cell burden) of each patient tumor was plotted onto the TIES map and actual clinical outcomes of LRC (green) and LRF (red) were evaluated with respect to their given TIES. Right panel, boxplots show patient tumors that achieved LRC had lower iRIS values compared to those with LRF (** represents P < 0.01). (C) Kaplan-Meier estimates for OS demonstrate patients with tumors classified as iRISlo vs iRIShi have improved OS (HR: 0.54, 95% CI: 0.28–1.0; P = 0.04). Boxplots show that patients who achieved LRC have (D) higher E0/S0 and E) lower C0/E0 ratios than those with LRF (*** P < 0.001).