Exhaustion (78) Self-tolerance (35) Shared (4) ACADM CIT HSPA8 MDFIC PLK4 SH3BGRL ADK HIST1H2BN RRM2 CCNB1 ASCC1 E2F8 IDH2 MKI67 PON2 SNRPB2 ANLN HIST1H3D SGOL1 LAG3 ATF1 EIF2S1 IFNG NDFIP1 PRKD2 SS18 AURKA ITM2A SNN TNFRSF9 (4-1BB) CCL4 ELL2 IL6ST NFIL3 PTPN6 SUPT4H1 CD81 KIF11 SPAG5 TOP2A CCND2 ENG IRF4 NFKBIZ RERE TACC3 CENPA KIF2C TCF19   CCR5 ENTPD1 ISG20 NR4A2 RNF11 TCF7 CHAF1B MARCKSL1 TFRC   CCT8 EVL ITGA4 NRP1 RPA2 TNFRSF1B CHST3 MCM2 TPI1   CD160 FAM102A ITGAE NUCB1 RSAD2 TTC3 FEN1 MCM6 XCL1   CD244 FAM134B JAK3 NXF1 SDHA UBR4 H2AFX PIF1 ZRANB3   CD7 FOS KLF10 OSBPL11 SELL VAMP7 HIST1H2BF PKM2     CD9 FYN KPNB1 PBX3 SERPINB9 WNK1 HIST1H2BH RAD54L     CHEK1 GZMK LBR PDK1 SFMBT2 ZFP36 HIST1H2BJ RCC1     CIRH1A HMGCS1 LCLAT1 PELI1 SGK1 ZFP91 HIST1H2BM RRM1

Table 1: Distinct core genes drive TILN enrichment of tolerance and exhaustion gene sets. Core genes differ in the leading edges of the exhaustion [5] and tolerance [6] gene sets compared to the TILN versus PBMC analysis [4]. Leading edge genes (circled in Figure 2A) are the core genes that drive the enrichment score, which is statistically significant for both the exhaustion and tolerance comparisons.