The top defining marker of cluster nAg.Bhlhe40- HiCd8 was Bhlhe40 (Figure 3G; Table S1), a transcription factor we previously demonstrated was upregulated in tumor-specific T cells and required for CD4 and/or CD8 T cell effector function and response to ICT.24 In addition to Bhlhe40 (as well as Pdcd1, Havcr2, and Lag3), this cluster notably expressed other transcripts induced by T cell receptor (TCR) activation (e.g., Ctla4, Cd69, Nr4a1, and Nr4a3) and displayed high expression of Tbx21 (T-bet) and Ifng (Figures 3G, 3H, and S6B). Here, CD4 is linked to neoplasm.