The CD4+ T-cell trajectory followed a similar pattern as CD8+ T cells, starting with naïve genes (SELL, TCF7, and IL7R), followed by genes for activation and effector molecules (CD44, CXCR3, and GZMM), and then by exhaustion-related genes (LAG3, EOMES, LAYN, BTLA, and IRF4) (Fig. 4I, J; Supplementary Fig. 6G), indicating cancer-driven exhaustion also of CD4+ T cells. The gene discussed is IRF4; the disease is cancer.