Extended Data Fig. 9: Ablation of KCa3.1 R350 methylation promotes T cell exhaustion in an in-vivo tumor and infection model.

a, Tumour weight of B16-OVA tumours isolated at D12 post transfer of OT-I T cells expressing KCa3.1^WT or KCa3.1^R350A. b, Surface expression of PD1⁺, Lag3⁺ and PD1⁺Tim-3⁺ in CD8⁺ TIL isolated at D12 post transfer into B16-OVA tumour-bearing mice of OT-I T cells expressing KCa3.1^WT or KCa3.1^R350A. c, d, Representative histogram of TOX expression and quantification (c) and of Tex^prog (CD69^loLy108^hi) (d) in CD8⁺ TIL expressing KCa3.1^WT or KCa3.1^R350A isolated at D12 as in (b). e, Representative contour plot (left) and quantification of IFNγ⁺TNF⁺ (right) in OT-I T cells expressing KCa3.1^WT or KCa3.1^R350A at D12 post transfer as in (b). f–h, Representative contour plot (f) and quantification (g) Tex^prog (Ly108⁺Tim-3⁻) and Tex^term (Ly108⁻Tim-3⁺) and CD62L⁺ (h) on congenically marked OT-I T cells expressing KCa3.1^WT or KCa3.1^R350A, mixed and transferred at a ratio of 1:1. TIL were isolated from B16-OVA tumours at D12 post T cell transfer. i, Gating strategy to identify transferred Thy1.1⁺ CD8⁺ T cells in spleen at day 9 post infection. j, Frequency of KCa3.1^WT- and KCa3.1^R350A -expressing P14 T cells in spleens, D9 post infection with LCMV-Clone-13. k, Frequency of TCF1⁺ cells in KCa3.1^WT- and KCa3.1^R350A -expressing P14 T cells in spleens, analyzed as in (i). l, Frequency of Tim-3⁻Ly108⁺ Tex^prog and Tim-3⁺Ly108⁻ Tex^term in KCa3.1^WT- and KCa3.1^R350A -expressing P14 T cells in spleens, analyzed as in (i). m, Frequency of Tim-3⁺Cx3CR1⁺PD1⁺ Tex^eff KCa3.1^WT- and KCa3.1^R350A -expressing P14 T cells in spleens, analyzed as in (i). (a, c, e, h–l: n = 4 mice/group; b, d: n = 3 mice/group; f, g: n = 7 mice/group) Data are mean±s.d. Unpaired two-tailed Student’s t-test (a–e) and paired two-tailed Student’s t-test (f, l).

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