Fig. 4. β2-adrenergic signaling modulates the abscopal effect via the egress of CD8+ T cells from the LN in the CT26 colon carcinoma model.
Growth of irradiated tumors (left) and non-irradiated tumors (right) in the mice housed at 22 °C (ST) or 30 °C (TT) that did or did not receive FTY720 a; or in WT or β2-AR KO mice which were irradiated and then did or did not receive FTY720 b; c CD8+ T cells in the draining LN of irradiated (left) and non-irradiated (right) tumors in irradiated β2-AR KO mice treated with/without FTY720; d–f Data from irradiated WT mice housed at 30 °C (left panels) and β2-AR KO mice (right panels) which received radiation with/without FTY720: expression of IFNγ+ d, TNFα+ e, and GzmB+ f; g–i the expression of CTLA-4+ g, PD-1+ and LAG-3+ h, PD-1+, and Tim-3+ i in non-irradiated tumors from irradiated β2-AR KO mice treated with/without FTY720. The expression of CXCR3 in non-irradiated tumors j and the level of CXCL9 in serum k was detected in irradiated β2-AR KO mice treated with/without FTY720. Data are presented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 (two-way ANOVA analysis for a, b; Student’s t test analysis for c–k). For a, n = 10 biologically independent mice in all groups; For b and c, n = 9 biologically independent mice in all groups; For d and f, n = 8 biologically independent mice in Rad + 30 °C group, n = 10 biologically independent mice in Rad + 30 °C + FTY720 group, n = 3 biologically independent mice in KO + Rad group, n = 4 biologically independent mice in KO + Rad + FTY720 group; For e, n = 8 biologically independent mice in Rad + 30 °C group, n = 10 biologically independent mice in Rad + 30 °C + FTY720 group, n = 4 biologically independent mice in KO + Rad group, n = 4 biologically independent mice in KO + Rad + FTY720 group; For g and j, n = 4 biologically independent mice in KO + Rad group, n = 3 biologically independent mice in KO + Rad + FTY720 group; For h, n = 5 biologically independent mice in KO + Rad group, n = 4 biologically independent mice in KO + Rad + FTY720 group; For i, n = 5 biologically independent mice in two groups; For k, n = 5 biologically independent mice in KO + Rad group, n = 3 biologically independent mice in KO + Rad + FTY720 group.