Fig. 5: Lenalidomide retrieves the antitumor function of YTHDF2-deficient CD8 T cells. | Nature Communications

Fig. 5: Lenalidomide retrieves the antitumor function of YTHDF2-deficient CD8 T cells.

From: YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity

Fig. 5

a Click-it RNA imaging and analysis of nascent RNA synthesis (green) in Ythdf2F/F (n = 5 independent samples) and Ythdf2CKO (n = 5 independent samples) CD8 T cells primed (anti-CD3/CD28, 5 μg/ml, 24 h) in the presence of 10 μΜ lenalidomide (len) or vehicle (veh). Scale bar, 10 μm. b Quantification of Ki-67 MFI among Ythdf2F/F (n = 4 independent samples) and Ythdf2CKO (n = 4 independent samples) CD8 T cells primed in the presence of 10 μΜ len or veh. c Click-it RNA imaging and analysis of nascent RNA synthesis (green) in Ythdf2F/F;OT-1 (n = 5 independent samples) and Ythdf2CKO;OT-1 (n = 5 independent samples) CD8 T cells primed (OVA, 10 nM, 24 h) in the presence of 10 μΜ len or veh. Scale bar, 10 μm. d Quantification of Ki-67 MFI among Ythdf2F/F;OT-1 (n = 5 independent samples) and Ythdf2CKO;OT-1 (n = 5 independent samples) CD8 T cells primed (OVA, 10 nM, 72 h) in the presence of 10 μΜ len or veh. e Quantification of Gzm B, IFN-γ MFI among Ythdf2F/F (n = 4 independent samples) and Ythdf2CKO (n = 4 independent samples) CD8 T cells primed (anti-CD3/CD28, 5 μg/ml, 48 h) in the presence of 10 μΜ len or veh. f MC38-bearing Ythdf2F/F (n = 21) or Ythdf2CKO (n = 18) mice were treated with anti-PD-1 (250 μg/mouse) and/or len (10 mg/kg) and monitored for tumor growth. g Hepa1-6 tumor-bearing Ythdf2F/F (n = 12) or Ythdf2CKO (n = 12) mice were treated with anti-PD-1 (250 μg/mouse) and/or len (10 mg/kg) and monitored for tumor growth. h Quantification of Gzm B+ CD8 T or IFN-γ+ CD8 T frequencies within TILs from Hepa1-6-bearing Ythdf2F/F (n = 6) or Ythdf2CKO (n = 6) mice treated with anti-PD-1 (250 μg/mouse) and/or len (10 mg/kg) (D13). Error bars, mean ± s.e.m. Two-way ANOVA (a–h).

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