Fig. 4
From: Targeting the orphan nuclear receptor NR2F6 in T cells primes tumors for immune checkpoint therapy
Acute CRISPR/Cas9 mediated gene ablation of Nr2f6 prior therapeutic adoptive transfer in combination with established CTLA-4 and PD-L1 immune checkpoint blockade. a Experimental scheme of tumor injection (d0), adoptive cell transfer therapy of CRISPR/Cas9 mediated Nr2f6 gene knockout CD3+ T cells (d3 and d10) and immune checkpoint blockade therapy (d3, d5, d7, d10, d14). b Tumor growth curve of wildtype mice injected with 5 × 105 MC38 tumor cells, treated with αPD-L1 (dashed lines) or IgG2b control antibody (continuous lines) in combination with no ACT (black), ACT with CD3CRISPR.NTC (blue, c) or ACT with CD3CRISPR.Nr2f6. (pink, d) CD3+T cells. f Tumor growth curve of wildtype mice injected with 5 × 105 MC38 tumor cells, treated with αCTLA-4 (dashed lines) or IgG control antibody (continuous lines) in combination with no ACT (black), ACT with CD3CRISPR.NTC (blue, g) or ACT with CD3CRISPR.Nr2f6. (pink, h) CD3+ T cells. e Survival analysis using a Kaplan Meier plot of wildtype mice treated with αPD-L1 resulting in 3/8 long-term survivor mice in the combinatorial therapy group with an ACT of CD3CRISPR.Nr2f6 T cells (p < 0.0001). i Kaplan Meier analysis of wildtype mice treated with αCTLA-4, resulting in 8/12 long-term survivor mice in the combinatorial therapy group with an ACT of CD3Crispr.Nr2f6 T cells vs. 4/12 survivors in the corresponding control CD3Crispr.NTC ACT group. Results shown are derived from at least two independent experiments