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Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical Natural Killer Cells
Robin L. Williams, Sarah Cooley, Veronika Bachanova, Bruce R. Blazar, Daniel J. Weisdorf, Jeffrey S. Miller, Michael R. Verneris Biology of Blood and Marrow Transplantation Volume 24, Issue 3, Pages (March 2018) DOI: /j.bbmt Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions
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Figure 1 Absolute CD3+ T cell count predicts likelihood of NK cell expansion at day +14. (A) Absolute lymphocyte count, (B) absolute CD3 count, and (C) absolute CD8 count before lymphodepleting chemotherapy in both patient groups. (D and E) Percent expression of CD3 and CD8 in control subjects compared with both patient groups before chemotherapy and at day +14 after haplo-NK cell infusion. (F) Percent distribution of T cell subsets in control subjects and both patient groups prechemotherapy. (G and H) Percent expression and median fluorescent intensity analysis of PD-1 and (I and J) Tim-3 within CD8+ T cells in control subjects compared with both patient groups prechemotherapy and at day +14. (K and L) Percent expression of PD-1hi and dual PD-1+Tim-3+ expression within CD8+ T cells in donor control subjects compared with both patient groups before chemotherapy and at day +14 after haplo-NK cell infusion. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Biology of Blood and Marrow Transplantation , DOI: ( /j.bbmt ) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions
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Figure 2 Impaired cytokine production prechemotherapy and elevated percent expression of key transcription factors in CD8+ T cells with most exhausted receptor profiles. (A) Percent IL-2, (B) TNF-α, and (C) IFN-γ expression in PD-1hi CD8+ T cells in control subjects compared with haplo-NK cell expanders and nonexpanders prechemotherapy. (D) Percent IL-2, (E) TNF-α, and (F) IFN-γ expression in dual PD-1+Tim-3+ CD8+ T cells in control subjects compared with haplo-NK cell expanders and nonexpanders prechemotherapy. (G and H) Percent T-bet and Eomes expression in PD-1hi CD8+ T cells in control subjects compared with haplo-NK cell expanders and nonexpanders at day +14 after haplo-NK cell infusion. (I and J) Percent T-bet and Eomes expression in dual PD-1+Tim-3+ CD8+ T cells in donors compared with haplo-NK cell expanders and nonexpanders at day +14 after haplo-NK cell infusion. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Biology of Blood and Marrow Transplantation , DOI: ( /j.bbmt ) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions
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