Skip to main content
Fig. 7 | Journal for ImmunoTherapy of Cancer

Fig. 7

From: Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts

Fig. 7

Nivolumab inhibits growth of a MSI-H CRC PDX that correlates with increased human T cells in the tumor compared to the untreated MSI-H CRC PDX or a less-responsive MSS CRC-PDX in hu-CB-BRGS mice. a, Human hematopoietic (hCD45+) chimerism in the blood prior to CRC MSI-H PDX implantation. b, Tumor growth curves of MDA-C099–203 CRC-PDX (MSI-H) implanted into humanized (left) or non-humanized (right) BRGS mice. Hu-CB-BRGS control group: n = 6 mice/10 tumors; nivolumab group: n = 8 mice/15 tumors. BRGS control group: n = 2 mice/3 tumors; nivolumab group: 3 mice/6 tumors. c, Tumor growth inhibition comparison in the hu-CB-BRGS MSI-H, BRGS MSI-H and hu-CB-BRGS MSS mice. d, Human hematopoietic (hCD45+) chimerism in the spleen of CRC-MSI-H bearing hu-CB-BRGS mice. e-i, Immune measurements, as assessed using flow cytometry, of TILs or spleen from CRC MSI-H implanted humanized mice treated (+) or not (−) with nivolumab. e, The number of human (hCD45+), T (hCD3+) and CD8 (CD3 + CD8+) T-cells in the TILs. f, The numbers of IFNγ-producing T cells in the TILs (gate: hCD45 + CD3+). The MFI of inhibitory receptors PD-1 (g) and Tim3 (h) on human T cells (hCD45 + CD3+). Human PBMCs served as control. i, The MFIs of PD-L1 expression on the CRC MSI-H PDX tumors excised from the humanized mice were determined on the hCD45-mCD45-Epcam+HLA-A,B,C+ population in the TILs. j, Tumor growth curves of CRC172 MSS PDX in hu-CB-BRGS mice (n = 4 mice/8 tumors per group). k, The number of hCD45+ cells in the TILs of either the MSS CRC172 PDX or the MSI-H MDA-C099–203 PDX grown in the hu-CB-BRGS. Open circles in MSS nivolumab treated mice represent tumors from the nivolumab-treated hu-CB-BRGS mouse harvested d10 after start of treatment, with the control mice, while closed blue circles are from the 3 treated hu-CB-BRGS MSS mice harvested on d30. All MSI-H bearing hu-CB-BRGS mice were harvested d23–24 after start of nivolumab. Each point represents data from the indicated organ from an individual hu-CB-BRGS mouse that was either untreated (−, black) or treated with nivolumab (+, blue), as indicated. P-values: * < 0.05, ** < 0.01, *** < 0.001, **** < 0.0001

Back to article page