Extended Data Fig. 4: In vivo rescue of HLA class II expression on exposure of relapsed leukemia to IFN-γ. | Nature Medicine

Extended Data Fig. 4: In vivo rescue of HLA class II expression on exposure of relapsed leukemia to IFN-γ.

From: Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation

Extended Data Fig. 4

a, HLA-DR expression on primary leukemia cells collected from UPN 17 at diagnosis (in red) and at relapse after allo-HCT (in blue), re-assessed before infusion in NSG mice (left side panel) and on the respective patient-derived xenografts (PDXs). The gray histograms represent the FMO control of AML blasts at diagnosis. For each histogram, the percentage displayed refers to the comparison with the relevant FMO control. Shown are results representative for two independent experiments with primary leukemias and with PDXs originated from UPN 17 leukemia at diagnosis (n = 3 per experiment) and at post-transplantation relapse (n = 4 per experiment). b, Layout of the in vivo experiment: AML blasts purified from UPN 17 at diagnosis (D-AML) or at relapse after allo-HCT (R-AML) were infused by tail vein injection into 4-week-old NSG mice. Mice were monitored weekly for leukemia engraftment and, on appearance in their peripheral blood of human leukemic cells, received the infusion of T cells collected and ex vivo expanded from UPN 17 donor. c, From left to right are shown results obtained in mice receiving only leukemia cells gathered from UPN 17 at diagnosis (n = 3), mice receiving only leukemia cells gathered from UPN 17 at relapse after allo-HCT (n = 4), mice receiving leukemia cells gathered from UPN 17 at diagnosis followed by donor T cell infusion (green arrow, n = 4) and mice receiving leukemia cells gathered from UPN 17 at relapse after allo-HCT followed by donor T cell infusion (green arrow, n = 4). The top panel row displays the absolute counts of circulating human T cells (in green) and leukemia cells in diagnosis (in red) or relapse (in blue) PDXs. The middle panel row displays the expression on the surface of PDXs of HLA class I (black dots) and HLA-DR (white dots) molecules. The lower panel row displays the concentration of human IFN-γ (in orange), TNF-α (in fuchsia), IL-6 (in green), IL-10 (in light blue) and IL-2 (in violet) measured in the peripheral blood of the mice during the experiment. All the data are displayed as mean ± s.e.m. Shown are results representative for two independent experiments.

Back to article page