Figure 4. Metformin treatment promotes TM generation and protective immunity following infection and tumor challenge.
(a,b) OT-I cells (<5000) from OTI-TRAF6-WT and OTI-TRAF6-ΔT mice (CD45.2) were transferred into CD45.1 recipients and immunized with LmOva. 8 days post-infection mice were injected daily with PBS (n=7–9 per group), metformin (n=7–9 per group), or rapamycin (n=5 per group) for three weeks and were then challenged with LmOva. Ova-specific responses of host and donor cells in the blood were measured 5 days post-challenge. Dot plot numbers reflect the percentages of total CD8 T cells that are host or donor-derived (Ova-specific). Bar graphs represent percent of CD8 T cells that are donor-derived (means ± standard error). *p values (comparing to PBS) = 0.015 (Met) and 0.000038 (Rap)(a), 0.0373 (Met) and 0.00028 (Rap)(b). (c) C57BL/6 mice were immunized and daily injections of metformin or PBS began 7 days post-infection. Three weeks later treatments ceased and mice were inoculated with EL4-Ova tumors. Tumors became palpable by 18 days post-inoculation and mice were euthanized when tumors reached 2cm. Graph reflects percent survival (n=9, metformin and n=8, PBS).