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Methods to Improve Adoptive T-Cell Therapy for Melanoma: IFN-γ Enhances Anticancer Responses of Cell Products for Infusion  Marco Donia, Morten Hansen,

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Presentation on theme: "Methods to Improve Adoptive T-Cell Therapy for Melanoma: IFN-γ Enhances Anticancer Responses of Cell Products for Infusion  Marco Donia, Morten Hansen,"— Presentation transcript:

1 Methods to Improve Adoptive T-Cell Therapy for Melanoma: IFN-γ Enhances Anticancer Responses of Cell Products for Infusion  Marco Donia, Morten Hansen, Sarah L. Sendrup, Trine Zeeberg Iversen, Eva Ellebæk, Mads H. Andersen, Per thor Straten, Inge Marie Svane  Journal of Investigative Dermatology  Volume 133, Issue 2, Pages (February 2013) DOI: /jid Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Association of clinical response and absolute number of in vitro tumor-reactive CD8+ T cells in infusion products for adoptive T-cell therapy (ACT). Infusion products were tested for reactivity against autologous melanoma cell lines (indicated with the arrow), or, when an autologous cell line was not available, against a panel of four to eight HLA-A-matched allogeneic melanoma cell lines (only the highest reactivity is shown). Data show that clinical response is associated with a higher absolute number of infused in vitro tumor-reactive CD8+ tumor-infiltrating lymphocytes. CR/PR, complete response or partial response; SD/PD, stable disease or progressive disease. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 IFN-γ increased autologous tumor recognition by CD8+ tumor-infiltrating lymphocytes (TILs). TILs were stimulated with autologous target melanoma cells as described in Materials and Methods. (a) Figure shows the frequency of cytokine-producing CD8+ TILs upon stimulation with autologous tumors in the left panel, and the difference for each sample (IFN-γ treated minus control) in the right panel. (b) Histograms and plots show, respectively, class I MHC expression and cytokine production by CD8+ TILs. Two TIL/autologous tumor pairs are depicted, representing an increase of tumor recognition associated with significant upregulation of class I MHC (upper panel) in a constitutively MHC I+ tumor and (lower panel) in a tumor with very low MHC I expression. Plots are gated on live CD8+ TILs. Dotted gray line, isotype. Solid gray line, untreated cell line. Solid black line, IFN-γ-treated cell line. CI, confidence interval; Pt., patient. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Effects of IFN-γ on autologous tumor recognition by CD8+ tumor-infiltrating lymphocytes (TILs) specific for defined tumor-associated antigens. TILs were stimulated with autologous target melanoma cells as described in Materials and Methods. Plots show the frequency of cytokine-producing CD8+ TILs of defined specificity (gray dots) or of undefined specificity (black dots) upon stimulation with autologous tumor cells. (a) Reduced recognition by MART-1-specific CD8+ TILs with concomitant increased recognition by CD8+ TILs of undefined specificity. (b) Increased recognition by MAGE-A1-specific CD8+ TILs and concomitant increased recognition by CD8+ TILs of undefined specificity. (c) Reduced recognition by TAG-specific CD8+ TILs with stable/reduced recognition by CD8+ TILs of undefined specificity. Pt., patient. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 IFN-γ increased autologous tumor recognition by CD4+ tumor-infiltrating lymphocytes (TILs). TILs were stimulated with autologous target melanoma cells as described in Materials and Methods. (a) Figure shows the frequency of cytokine-producing CD4+ TILs upon stimulation with autologous tumors in the left panel, and difference for each sample (IFN-γ treated minus control) in the right panel. (b) Histograms and plots show, respectively, class II MHC expression and cytokine production by CD4+ TILs. Two TIL/autologous tumor pairs are depicted, representing an increase of tumor recognition associated with significant upregulation of class II MHC molecules of tumors (upper panel) constitutively MHC II+ or (lower panel) MHC II−. Plots are gated on live CD4+ TILs. Dotted gray line, isotype. Solid gray line, untreated cell line. Solid black line, IFN-γ treated cell line. CI, confidence interval; Pt., patient. Journal of Investigative Dermatology  , DOI: ( /jid ) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

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