Fig. 5: Inactivating UHRF1 induces memory formation via expansion of T cell clones with low-affinity TCRs and synergizes with anti-CTLA4-based ICB therapy.

a, b Survivor mice that rejected Uhrf1-knockout tumors were rechallenged parental LG1233-OVA cells. Tumor growth (a) and survival (b) curves were plotted. n = 5 each group. c Frequency of high- and low-affinity TCR clonotypes in tumors from mice injected with sgNT or sgUhrf1 LG1233-OVA cells. n = 5 per group. d Schematic representation of T cell therapy. e, f Tumor growth curves of LG1233-OVA (N4) (e) or LG1233-OVA (Q4) (f) cells injected into male C57BL/6 mice. n = 5 per group. g, h Tumor growth (g) and survival (h) curves of female mice with shNT or shUhrf1 tumors treated with anti-CTLA4 on days 7, 10 and 14. n = 6 per group (g). n = 10 (shNT+IgG), 8 (shNT+anti-CTLA4), 6 (shUhrf1 + IgG), 8 (shUhrf1+anti-CTLA4) (h). g, h were performed independently. i Rechallenge of survivor mice from (h) with parental LLC-OVA cells. n = 5 (control), 4 (survivor). j–n TCRβ sequencing for LLC-OVA tumors. TCR similarity (j–m) and expanded TCR clones, constituting >10%, >5%, >2%, >1%, and >0.5% are shown as gradient segments (n). n = 6 (shNT+IgG, shNT+anti-CTLA4 and shUhrf1 + IgG), 5 (shUhrf1+anti-CTLA4). Data are mean ± SEM (a, c, e–g, i). Box plots (j–m), the horizontal lines indicate the first, second (median) and third quartiles; the whiskers extend to ±1.5× the interquartile range. n indicates the number of biological replicates. P values were determined using two-way ANOVA test (a, e–g, i), log-rank test (b, h), two-tailed Student’s t test (c, j–m) and Chi-square test (n). AA, amino acid. Source data are provided as a Source Data file.