Figure 6: Senescent-stromal driven increases in G-MDSCs suppress CD8+ T cells and promote tumour growth.
From: Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis
(a) Representative whole body images of PDSC5 tumour cells co-injected with MSFs as indicated following Ly6G depletion (or control). Non-senescent (Non-Sen) MSFs with PDSC5 cells (left), senescent MSFs (Sen) with PDSC5 cells (middle), and senescent MSFs with PDSC5 cells depleted of Ly6G+ cells (Sen+αLy6G) (right) on day 9 post injection. Sen mice received IgG antibody as a control. Scale for photon flux is shown to the right of the image. (b) Effect of Ly6G+ cell depletion on tumour growth in Non-Sen or Sen subcutaneous co-injections with PDSC5 tumour cells. Mice were treated I.P. with a neutralizing Ly6G antibody (or control IgG) every 3 days. Live imaging analysis of day 9 growth is represented as MPF+s.e.m. *P value <0.05, Student’s t-test. n=7–8. (c) Effect of Ly6G+ cell depletion on tumour growth in Non-Sen or Sen subcutaneous co-injections with MK16-Ras tumour cells. Mice were treated I.P. with a neutralizing Ly6G antibody (or control IgG) every 3 days. Data are presented as mean tumour area (mm2)+s.e.m. at day 26 post injection. *P value <0.05, Student’s t-test. n=14–18. (d) Effect of CD8 depletion on tumour growth in Non-Sen or Sen subcutaneous co-injections with PDSC5 tumour cells. Mice were treated I.P. with a neutralizing CD8 antibody (or control IgG) twice weekly. Tumour growth was assessed by live imaging analysis. Data are presented as mean fold growth+s.e.m. *P value<0.05, Student’s t-test. ns is not significant. n=9–10. (e) CD8+ and Ly6G+ cell depletion in mice bearing PDSC5 tumour co-injections. Mice were treated I.P. with one out of three dosing regimens: IgG, αLy6G or αCD8+αLy6G. αCD8 was given twice weekly and αLy6G was given every 3 days for the duration of the experiment. Mice were subcutaneously injected with Non-Sen+PDSC5 or Sen+PDSC5 and tumour growth was assessed by live imaging analysis. Data are presented by mean fold growth+s.e.m. *P value<0.05, Student’s t-test. ns is not significant. n=5–10. MPF, mean photon flux.
