Disruption of functional Bcl6 gene in growing AITL-like tumors leads to tumor regression. (A) Exemplary immunohistochemistry sections of AITL patient samples depicting CD3 and Bcl6 expression. (B) Representative flow cytometric plots showing subsets of CD4 cells based on expression of PD-1 and CXCR5. (C) Comparing frequencies of CD4⁺CXCR5⁺PD-1⁺ cells between tumor-free, nontumorous (non-tumor), and tumorous (tumor) samples (n = 11 tumor-free; n = 15 nontumorous; and n = 21 tumorous samples). (D) MFI of CXCR5 and PD-1 on CD4⁺CXCR5⁺PD-1⁺ cells (n = 11 tumor-free; n = 15 nontumorous; and n = 21 tumorous samples). Bcl6 expression in CXCR5⁻PD1⁻, CXCR5⁺PD-1⁻, and CXCR5⁺PD-1⁺ cells from tumor samples (E) and Bcl6 MFI of CD4⁺CXCR5⁺PD-1⁺ cells (F) (n = 9 tumor-free; n = 12 nontumorous; and n = 13 tumorous). (G) Representative histogram and frequency of Ki-67 levels in tumor CD4⁺ subsets (n = 21 tumorous). (H) Roquin^san/+ mice were bred with a CD4-specific, tamoxifen-inducible Cre-recombinase to target the Bcl6 gene (Roquin^san/+; Cd4-Cre^ERT2+/−; Bcl6^f/f). Representative time course (I) and sonograms (J) demonstrating tumor regression in mice with Bcl6 gene deletion (n = 5 Roquin^san/+; Cd4-Cre^ERT2+/−; Bcl6^+/+; n = 6 Roquin^san/+; Cd4-Cre^ERT2+/−; Bcl6^f/f). Error bars in panels C-G,I represent the SEM. Data are pooled from at least 2 independent experiments. *P < .05; **P < .01; ***P < .001; ****P < .0001.