PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model
Fig 5
T cells are required for the therapeutic effect of PD-1/CTLA-4 blockade in EBV-infected humanized mice.
A. Human T cells were harvested at 4 weeks post-injection from spleens of EBV- infected mice that were PD-1/CTLA-4 Ab treated, or treated with istoype control Abs. The T cells were incubated for 72 hr in medium containing IL-2, then exposed to autologous umbilical cord mononuclear cells in the presence of vehicle control (shown as a peptide concentration of "0"), a mixture of synthetic EBV peptides (“EBV peptide”), or a mixture of CMV peptides (“CMV peptide”), and IFN-γ secreted into the culture supernatant was quantified by ELISA. The plot shows the means of 3–6 replicates for each condition with error bars indicating the standard deviations. The p value shown (calculated by a 2-tailed student's t test) is for the IFN-γ values produced by T cells against the EBV peptide. B. NSG mice were injected i.p. with EBV-infected cord blood cells and then treated with or without anti-PD-1/anti-CTLA-4 antibodies, in the presence of the OKT3 T-cell depleting ab (6 mice/group). Mice were euthanized 26 days post-injection. Grossly visible lymphomas were dissected and weighed. The weight of tumors is normalized to the average size of the tumors not treated with PD-1/CTLA-4-abs (set as 1).