Fig 1: Rapid Intratumoral and Progressive Systemic Dysfunction of Neoantigen-Specific T Cells(A) Frequency of PD-1, Lag3, Tim3, and TIGIT expression by tetramer+ T cells in the spleen (Spl) and tumor (Tum) at day 22 post-tumor implantation. Each dot is an independent mouse, and data are mean ± SEM. *p < 0.05, **p < 0.05, and ***p < 0.005 (one-way ANOVA, with a post hoc test to correct for multiple comparisons).(B) Representative plots of markers quantified in (A).(C) Mean frequency of CB101–109:H-2Db-specific CD8+ T cells that express none (0), one (PD-1), or co-express 2, 3, or 4 inhibitory receptors at day 22.(D) Proportion of total CD8+ T cells producing IFN? following ex vivo re-stimulation with CB101–109 peptide at day 22.(E) Number of tetramer+ T cells producing IFN? at day 22. Data are mean ± SEM, and each dot is an independent mouse. *p < 0.05 (one-way ANOVA, with a post hoc test to correct for multiple comparisons).(F) Progressive phenotypic and functional changes in splenic tetramer+ CD8+ T cells in mice bearing KPC2a tumors ± aPD-L1. Data are mean ± SEM. n = 4 or 5 mice per group.(G) Progressive phenotypic and functional changes in intratumoral tetramer+ CD8+ T cells. Data are mean ± SEM. *p < 0.05 (unpaired two-tailed Student’s t test). n = 4 or 5 mice per group.(H) Analysis of the indicated antigens on circulating tetramer+ T cells following aPD-L1 treatment. Data are mean ± SEM. n = 4 or 5 mice per group. See also Figure S4.