Figure 4.

TGF-β blockade enhances the activation of TILs in the fragments as induced by anti-CD137 in combination with anti-PD-1 plus anti-CD137 agents.

a) Scheme of the experiments in which fragments were cultured under the indicated conditions using the 1D11 antibody to neutralize TGF-β. b) Levels of TGF-β as detectable in the supernatants of the tumor-derived fragments in culture (left) that correlate positively with IFNγ concentrations in pooled supernatants from the same mice (right). c) Levels of IFNγ in the supernatants of the fragments cultured under the indicated color-coded conditions. d) (Left panel) Mean fluorescence intensity of Ki67 as a marker of CD8⁺ cell proliferation in gated permeabilized cell suspensions of the fragments cultured under the indicated color-coded conditions. (Right panel) Percentage of granzyme B⁺ cells among CD8⁺ T cells in the fragments at the end of the culture under the indicated color-coded conditions. MDTFs: mouse-derived tumor fragments. MFI: mean fluorescence intensity.