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. 2016 Feb 17;7:10501. doi: 10.1038/ncomms10501

Figure 3. Sequential anti-TIM-3 blocking displays clinical efficacy in anti-PD-1 adaptive resistant tumours.

Figure 3

(a,b) Survival after PD-1 blockade alone (anti-PD-1 resistant) or PD-1 and sequential TIM-3 blockade combination treatment (PD-1 alone: n=16 and sequential combination treatment: n=11) (P=0.0008) after documented tumor burden. Treatment started at week 0. Median survival PD1 5 weeks vs PD-1+TIM-3 sequential treatment 11.9 weeks. (c) Representative flow cytometry data of IFN-gamma expression in CD8 T cells from anti-PD-1 resistant (PD-1R) and sequential anti-PD-1 plus anti-TIM-3 combination (Seq CombS): 2 weeks′ anti-PD-1 and anti-TIM-3 combination treatment after development of resistance to PD-1 single treatment. Fluorescent conjugated anti-TIM-3 antibody is the same clone (RMT3-23) as the therapeutic antibody. (d) IFN-gamma and Ki-67 positive CD8 T cell counts from anti-PD-1 resistant (PD-1R) (n=6) and sequential anti-PD-1 plus anti-TIM-3 combination (Seq CombS) (n=6) (*P<0.05, **P<0.01). (e) IL-6 and PGRN production in BALFs from PD-1R (n=6) and comb (Seq CombS: n=6) (*P<0.05). Data are shown as mean±s.d., P values are calculated using student's t test for all data except for the survival data.