Supplementary Figures S1-S16 from Tumor-associated NK Cells Regulate Distinct CD8+ T-cell Differentiation Program in Cancer and Contribute to Resistance against Immune Checkpoint Blockers

Supplementary Figure S1 shows PD-1 blockade therapy combined with NK cell depletion improves tumor control and increases CD8⁺ T cell infiltration. Supplementary Figure S2 shows the combination of NK cell depletion and ICB is most effective when NK cells are depleted at an early stage. Supplementary Figure S3 shows NKRT accumulation is tumor-site specific. Supplementary Figure S4 shows phenotypic changes in CD4⁺ T cells upon NK cell depletion. Supplementary Figure S5 shows NKRTs are antigen-specific and exhibit enhanced tumor-controlling efficacy when combined with ICB. Supplementary Figure S6 shows NKRT formation depends on the timing of NK cell depletion. Supplementary Figure S7 shows NK cell depletion delays CD8⁺ T cell exhaustion in day 15 MC38 tumors. Supplementary Figure S8 shows NK cell depletion delays CD8⁺ T cell exhaustion in day 20 MC38 tumors. Supplementary Figure S9 shows NK cell depletion improves tumor control in the ACT setting. Supplementary Figure S10 shows distinct gene expression profiles in CD8⁺ T cells following NK cell depletion. Supplementary Figure S11 shows volcano plots of differentially expressed genes under specific conditions. Supplementary Figure S12 shows elevated p-STAT3 and p-STAT5 levels in CD8⁺ T cells from NK cell-depleted tumors. Supplementary Figure S13 shows cytokines play a critical role in NKRT formation and anti-tumor activity. Supplementary Figure S14 shows computational model fits of tumor growth curves and CD8⁺ T cell dynamics. Supplementary Figure S15 shows phenotypic variation in tumor-infiltrating NK cells across tumor models. Supplementary Figure S16 shows expression patterns of tissue-resident markers in CD8⁺ T cells and NK cell proportions in responders versus non-responders to immunotherapy.